This study was planned to investigate the effects of seaweed supplementation, genetic strain, heat stress and their interactions on laying hen performances, blood chemistry and hematology. In a short-term trial, laying hens of the two genetic lines Lohman LSL-Lite (White) and Lohman Brown-Lite (Brown) were supplemented with Chondrus crispus (CC) at 3% for 21 days, while a control group was not. In a long-term trial, the same two strains were assigned to control (0%), 3% red seaweed Chondrus crispus (CC) or 0.5% brown seaweed Ascophyllum nodosum (AN)-supplemented diets for 41 weeks, concluding with a four-week control or heat-stress period. The White hens displayed higher egg production and a lower feed/egg ratio. The short-term inclusion of CC significantly reduced the feed intake, weight gain and feed/egg ratio. The long-term seaweed intake affected the plasma albumin and gamma-glutamyl transferase (GGT) (p < 0.05), and there were significant strain-heat stress interactions; heat stress in the Brown birds was associated with reduced protein, globulin and glucose and increased cholesterol and GGT levels and higher heterophil-to-lymphocyte (H/L) ratios (p < 0.05) in response to heat stress (p < 0.05). In conclusion, a long-term seaweed supplementation affected the plasma protein and enzyme profiles, yet had little effect on hen leukocyte counts and the overall performance.