Several factors may influence numbers and function of peripheral blood lymphocytes (PBLs) by different processes. We conducted this study to evaluate the effect of E-CAB-94011 and E-JUR-94013, two marine fish extracts from S. scombrus and T. trachurus, respectively, on in vitro PBLs activation and on the expression and functionality of Fas, a cell surface molecule that plays a central role in immune homeostasis and cytotoxic activity. PBLs from 24 healthy volunteers were isolated and flow cytometry was performed to measure the state of activation, Fas expression and apoptosis of PBLs. Functionality of Fas was tested by assessing apoptosis after incubation of isolated lymphocytes with agonistic anti-Fas antibodies in blood samples treated with both E-CAB-94011 and E-JUR-94013. Studies on the lymphocyte cell marker suggest a clear immune activation as measured by the increased levels of CD25, CD8, CD38, CD19 and HLA-DR in vitro expression on lymphocytes treated with both extracts. In addition, a significant reduction in the percentages of apoptotic CD19(+)CD38(+) double positive lymphocytes could be demonstrated in the treated samples with respect to controls (p<0.05). Therefore the present results indicate that both E-CAB-94011 and E-JUR-94013 in vitro are powerful immunoregulatory, increasing immune surveillance.