Ulva lactucais a seaweed with antinutritional cell wall for monogastrics. Carbohydrate-Active enZymes (CAZymes) supplementation can potentially cause its disruption. This study evaluates four diets: Ctrl—control diet; UL—control + 7%U. lactuca(wild caught, powdered form); ULR—UL + 0.005% Rovabio®Excel AP; ULU—UL + 0.01% ulvan lyase on piglets’ haematologic and serologic profiles, hepatic lipids and minerals. White blood cells and lymphocytes reached the highest values in piglets fed UL compared to control, and to control and ULR; respectively (P< 0.05). IgG levels were boosted by seaweed incorporation compared to control (P= 0.015). The glycaemic homeostasis was assured by the seaweed inclusion. Dietary seaweed decreased serum lipids (P< 0.001), with the exception of ULU, due to HDL-cholesterol increase (P< 0.001). Cortisol was decreased in ULR and ULU (P< 0.001). No systemic inflammation was observed (P> 0.05). While hepaticn-3 PUFA increased in piglets fed with seaweed diets due to increment of beneficial 22:5n-3 and 22:6n-3 fatty acids (P< 0.05), the opposite occurred forn-6 PUFA, PUFA/SFA andn-6/n-3 ratios (P< 0.05). Hepatic pigments were unchanged (P> 0.05). ULR reduced α-tocopherol levels (P= 0.036) and increased serum potassium levels (P< 0.001) compared to control. Seaweed contributed to overcome piglets’ weaning stress, with some benefits of including CAZyme supplementation.