Portosystemic shunt (PSS) is a vascular disease that can be treated by various surgical techniques. Current veterinary studies are evaluating new prognostic markers in dogs with PSS. This study aims at evaluating the prognostic value of plasma protein C activity in dogs (n = 34) with PSS treated surgically using an ameroid constrictor. Plasma protein C activity was measured in the following time periods: preoperatively (T1), 2 days after surgery (T2), 8 weeks after surgery (T3) and > 6 months after surgery (T4). There was a significant increase in plasma protein C activity between T1/T2 and T3/T4 (P < 0.001). There was no significant relationship between the plasma protein C activity and sex (P = 0.676), age (P = 0.172), breed (P = 0.573), type of clinical signs (neurological P = 0.993; gastrointestinal P = 0.924; urological P = 0.385) and type of portosystemic shunt (P = 0.516), except for dogs with a caval type of extrahepatic PSS termination that had significant lower plasma protein C activity values compared to dogs with a diaphragmatic type of extrahepatic PSS (P = 0.031). No significant relationship was found between plasma protein C activity and the probability of the dog's death (P = 0.334) or the dog's clinical outcome (P = 0.960). Although not a prognostic factor, protein C activity is a laboratory marker that is useful for the diagnosis of PSS in dogs and can also be helpful in the postoperative monitoring.