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Season 3 begins with Sarah pursuing the missing Helena who is being held in a faraway compound. Sarah uses her wiles and acting chops to deter a Topside investigator who threatens the Leda sisters' lives.
Castor pursues the Leda clones for original tissue samples. Meanwhile, Helena, who is pregnant and imprisoned, is examined by a mysterious villain.
Leda and Castor are both on the hunt for original clone DNA. On the lam, Mark and Gracie pursue new leads to find the samples that might set them free, while Art and Sarah reunite to track them down. Meanwhile, Cosima and Scott try to learn more about Castor's biology and Alison's new money-making venture is going gangbusters. A shocking revelation about the Castor-Leda connection leaves the sisters reeling, just before Sarah witnesses a deadly Prolethean-Castor face-off.
Mark is taken down in a Prolethean shoot-out and Sarah must step in to help. But as Sarah gathers intel that puts her on the trail of the original Castor DNA, a familiar foe is not far behind. While Helena continues to toil in a faraway military compound, it is ultimately Sarah's fate that will hang in the balance as she tries to save her sister. Meanwhile, Gracie is cast out from the Prolethean fold, and Alison and Donnie come face-to-face with unhappy drug lord, Jason Kellerman.
Helena and her seestra are reunited at the Castor camp when Sarah is captured. As Sarah suffers testing, Paul appears to chide her; but his allegiances are beginning to strain. While the Leda family worries about Sarah's absence, Gracie ‘breaks Amish' under the care of Mrs. S and an unwilling Felix. Cosima falls hard for an internet date, Shay.
Paul is pushed into action when he discovers the ugly truth behind the Castor Boys' logbooks of names. Meanwhile, Felix becomes desperate for information on Sarah's whereabouts and presses the still-ailing Rachel for any shred of a lead.
Alison must secure a store front in order to take her and Donnie's business to the "next level." But things don't go according to plan when her mother, Connie, proves to be a major hindrance. Cosima is facing familiar health issues and calls upon beleaguered Alison for a favor. But with Alison working to save an imperiled Donnie from the merciless hands of a drug lord, it's Cosima who ends up doing a favor. An unassuming Scott gets closer to the greatest discovery of all, when he sits down with beleaguered clone Rachel.
When Rachel makes a promise to Sarah, it comes with a hefty price. Meanwhile, Helena and Gracie work with the Hendrixes, and Donnie takes Kellerman to task. Over at Castor, Coady and Benchman scheme to track down the Castor Original, and Rudy descends on DYAD for a much needed asset.
Clone Club heads to London to track down the Castor Original, but their enemies follow closely.
Kendall may be the key to stop Castor; the sisters appear to be thwarting their most dangerous foe.