When skeletal remains are found at a construction site, the ownership is traced to a man who is a dead ringer for John.

When a young boy Wesley and his mother approach John Doe claiming that sperm bank records indicate he is the boy's father, John is pulled into a mystery as he tries to track down the list of donors and finds two of them dead, their brains removed.

High school kids are surprised by a bright light in the forest and an astronaut who walks toward them that they shoot. The police and John investigate and determine the astronaut actually died of a lack of oxygen resulting in cyanosis but a Colonel Dunagan moves in and take the body — John taps into satellite photography and sees a blast pattern that matches the one on Horseshoe Island that accompanied his arrival. John, Digger, and Frank sneak into the woods to examine the site and find a large pod. The pod is a Mars environmental test system and inside the trashed interior are a bunch of astronauts dead just like the first astronaut — then they get sealed in. Meanwhile Avery pursues her own investigation despite the military government and after interviewing Dunagan's staff sergeant, believes Dunagan is involved. The men start sniping at each other due to cyanosis symptoms while Stella and Avery track them down. John uses its navigation beacon to send out a SOS. The Staff Sergeant is...

Ken Rothman, an ex-police officer that Avery got fired for beating a suspect, gets into the police HQ by faking his death and he and his men quickly take the station and most of the staff (except Frank) hostage. Rothman demands his reputation be cleared, but John manages to get free and escape into the building, and soon discovers Rothman has a supply of Russian-made smallpox. John manages to take out a few terrorists before being recaptured and Rothman leaves John and Avery behind with a shattered vial of smallpox. It's fake, but the whole thing is a ploy to get hold of smallpox vaccine to sell as a bio-weapon. Doe figures it out and they capture Rothman just in time.

John is hit by lightning on his chest-brand and can see in color — going to see a fresh body, John realizes he's also lost access to his vast supply of knowledge and all the physical talents it provided. It's not a good time as a killer strikes, leaving a kidney from his victim with the promise of more to come. The killer strikes again with two killings as John tries to come to terms with his newfound ignorance and the loss of his money when he can't call the shots for his broker. John is bitter and reluctant to admit his newfound loss to anyone, and a disappointed killer threatens to come after him. It turns out that two women, sisters, are working as the killers and lure John into a trap — fortunately John figured the killer(s) were women and he'd be targeted and the police have him wired and are watching. While pursuing one of the killers John is hit with electricity again and is back to being color-blind and super-smart.