Noncorporeal aliens inhabit the bodies of Enterprise crew members to study how the crew reacts to a lethal virus infection that has afflicted Trip and Hoshi.
Enterprise escorts Tellarites to peace talks with Andorians. While transporting they rescue Andorians and say the Tellarites attacked them. Enterprise is soon attacked by an Andorian ship, and Archer must prove who is responsible.
While Enterprise is visiting Earth, Phlox is abducted by the Klingons and forced to research a cure for a virus destined to wipe out the race. Reed is tapped by a secret agency and ordered to betray Archer. Trip transfers to the Columbia.
While Enterprise tries to bring Trip on board to reverse the malicious Klingon modifications, Phlox and Antaak find a cure for the virus that will not please General K'Vagh.
Set in the dark and oppressive Mirror Universe, Commander Archer leads a mutiny in a bold attempt to seize control of an advanced starship - a vessel from the future that may be the key to saving the Terran Empire.
The Mirror Universe saga concludes as Archer declares himself captain of a formidable starship from the future, while his alien crew launch a rebellion in a desperate bid to keep him from achieving ultimate power.
While attending a conference on a proposed interplanetary alliance, Trip and T'Pol find out from a dying woman that they have a baby. Investigation shows the woman was a member of the xenophobic organization Terra Prime.
Paxton threatens to destroy Starfleet Headquarters if all aliens don't leave Earth. Enterprise must shut down the verteron array on Mars, but it is extremely well defended.