On the day of convicted serial killer-rapist John Mathers's execution, a new case following his MO causes a stay after countering the already administered lethal injection and urgent forensic (re-)examination. It was Catherine's first case leading to death row. The most modern techniques, even requiring federal equipment not available to Greg, show another killer was at work and probably one was a copy-cat, but the question remains in which order, as that may or not discharge Mathers.

Matt Phelps sends his two kids to bed, and out of the blue, there is a drive-by shooting and his daughter Aimee is shot and killed in her bed. Grissom, Warrick and Capt. Brass investigate the case and Grissom learns that Matt Phelps is Warrick's mentor and friend. Warrick's investigation is conducted based on his emotions instead of on the evidences with serious consequences for Matt and a suspect. Meanwhile, Nick and Sam Vega investigate the mysterious death of a boss of a four-men Internet service company in the air-conditioned servers' room. They find many secrets in the team but no suspect and no murder weapon. Until Nick observes the duct of the air-conditioning.

When Joanne Crooks is assaulted without rape at home, Catherine, Grissom, Nick, Warrick and Capt. Brass assume the investigation. They find fingerprints on the windows and they learn that the criminal is escalating in his crimes. They fear that he soon will rape his victim since this was his first break in. Meanwhile, Sara learns that the paraplegic prosecutor Melissa Winters will be submitted to a surgery of high risk. Three years ago, Winters was shot on the neck in a home invasion where her husband as killed, but the murderer has not been found. Now the bullet has moved and she needs the surgery. Sara decides to reopen the cold case using the bullet withdrawn in the surgery to try to find the criminal.

A man is found stabbed to death in an art house cinema while a young shooting victim is found in a storage room with a bizarrely wide bullet hole pattern.

A couple of high school students find the body of a woman in the press box of football field. Grissom, Nik, Sara and Capt. Brass investigate the case and they learn her identity, the waitress Alison Carpenter. Their further investigation lead them to the former prison inmate Jason Kent, who has recently been released. Alison was his girlfriend and was having sex with the drug dealer Jesus to postpone the debt of Jason with him. Meanwhile, Greg's DNA laboratory explodes and Sara and him are injured. Warrick and Catherine are assigned to investigate the case and find the responsible for the accident.

A team of robbers heist the First Monument Bank and Detective Cyrus Lockwood is shot and murdered. The team investigate the case and find that the thieves wanted a specific safety deposit box in the vault. Meanwhile the driver of the getaway van is found dead in the vehicle, Larry Whiting. He was a former valet of the Rampart Casino, owned by Sam Braun. When they find the name of the owner of the stolen box, Benny Murdock, an Catherine recognizes the name.

Several couples are killed bloodily after a wild party night in the same luxury hotel with Cameron and Mandy Klinefeld, or rather one somehow forced to kill the spouse. Nick is pleased to bump into former college mate Kenny Richmond, who works there, until it seems buddy boy passed confidential information to the press, which could get Nick fired.

Fingerprints suggest a link between two home invasions, but it's hard to link either the victims or the logical suspects, who may all be innocent. The crucial survivor testimony proves the most tenacious problem. A toddler found and accidentally fired a murder weapon in the family's suburb garden. Its place is a mystery, being so overt and unrelated to the victim, a bounty-hunting has-been, until the team consults the sky.

Because Warrick naively assumed simple uniformed cop Hal Watson would have arranged a search warrant, the crucial weapon in the rape and murder trial on a neighbor against Michael Fife is dismissed as evidence in court. A.D.A. Jeffrey Sinclair can only get a 24 hours delay to present new evidence to build the case again. Nick brilliantly smooths emotional waywardness from Sarah and Warrick. New clues expected to reconstruct the case against Fife actually indicate he's probably innocent. An alternative culprit must be found, starting from Fife's car where the bloody knife was planted.

When the nurse Debbie Marlin is found murdered in her bathroom, the CSI team investigates the case. They learn that Debbie was a promiscuous woman that used to date doctor. Her last boyfriend Dr. Michael Clark is missing and becomes the prime suspect of murdering her. However, their further investigation finds pieces of his body in plastic bags in several trash bins in an alley. Dr. Robbins concludes that the cuts have been made by a surgeon using probably a scalpel.

During the police marathon in Las Vegas, Grissom sees a runner outside the road and drives his car to the place, leaving Catherine alone. He finds a police officer dead. Dr. Robbins find that the victim was in excellent shape, but he had ingested two substances that combined killed him. Meanwhile, Sara, Warrick and Det. Louis Vartann investigate the murder of officers Manny Senteno and Patricia Fielding in a hotel room. Warrick's first impression is that might be a murder-suicide case. Soon they find fingerprints of the police officer Lydia Lopez and learn that she was lodged in the next-door room. When they look inside the room, it is completely trashed. Lydia says that she had sex with a Manny once a year during the marathon and she believes that her husband Archie Lopez might have followed her and trashed her room, but would never kill Manny and Patricia.

Greg has found a replacement in the DNA lab, Chandra Moore, and introduces her to the co-workers. Capt. Brass, Grissom and Greg, in his first case, investigate the death of an unidentified victim with a shot in the forehead in a shooting in the nightclub owned by Manny Brazil. He says that he does not know how the gun has passed through the metal detector. Catherine and Det. Louis Vartann investigate the murder of a woman covered in blood in a hotel room. The man, Carl Johnson, also covered in blood, tells to the detectives that he has never seen that woman before. Soon they learn that the victim is the stripper Nicole "Raven" Richards that drugged Carl to rob him. Warrick and Det. Chris Cavaliere investigate the death of Lance Frazer, a loser that died in the bathtub electrified by heat exchanger causing a short circuit in the motel. Soon Warrick learns that Lance hit a fifty-thousand-dollar jackpot on the previous night. Nick, Sara and Det. Travis investigate an "alien" buried in a shallow grave near the Area 51.

When a group of fraternity members find a spot covered by maggots, Grissom investigates the scene and believes a student is providing the flesh to the maggots. Based on the uniform size of the bones and woods, Nick and Grissom believe a mulching machine was used to discard the body, and soon they find evidence in the machine. Based on a fingernail found in a garbage bag, Catherine concludes that the Blue Painter Killer is back. Now the entire team is working on the case.

When a Hummer in the wrong way runs over an old Fiero, Grissom meets Capt. Brass to investigate the scene. He learns that the Hummer's driver has fled and the Fiero's driver is alive in the hospital. At a car convention, when the host Mr. Daluca opens the curtains to show the latest RV model to the audience, there is a dead woman. Warrick and Det. Louis Vartann learn that the victim is the twenty-nine-year-old model Lisa Schumacher. Dr. Robbins tells Catherine that Lisa was asphyxiated and she had sex before her death. Daluca becomes their prime suspect. Meanwhile, the model Gwen that is working at the convention, goes to the house of her personal trainer Paul Charles to workout and sees him dead through the window. Greg and Sara investigate the crime scene while Dr. Robbins carries out the autopsy. When he sees a black substance in his eye, Hazmat takes Sara and Greg to the decontamination shower. When the body of a boy is found on a bus stop bench covered by a blanket in front of a laundromat, Nick investigates the case. Dr. Robbins tells Nick that the cause of death was asphyxia from heat damage. They identify the victim is Chase Ryan and Nick tries to understand what might have happened to the boy.