Background: Stimulation of the immune system against disease and restoration of immune functions in immunodeficiency disease state are essential for maintaining good health. Objective: This study investigated the immunomodulatory effects of the leaf extract and fractions of Musanga cecropioides in immunocompetent and immunocompromised animal models. Methods: Humoral immune stimulatory effect of the extract and its fractions at 200 mg·kg?1 and 400 mg·kg?1 against sheep red blood cells (SRBCs) antigen was determined in both immunocompetent and cyclophosphamide (80 mg·kg?1) induced immunosuppressed animals. The effect of the most active fraction on leucopoiesis was also determined following high dose cyclophosphamide (300 mg·kg?1) suppression of the immune system. Levamisole at 2.5 mg·kg?1 was used as the reference drug throughout the study. Results: The extract dose dependently stimulated the humoral immune response to SRBC antigen in immunocompetent animals; however, its stimulatory effect was not significant (P > 0.05). In the immunosuppressed model, the extract at 400 mg·kg?1 evoked significant (P < 0.05) increase in antibody titer value with a corresponding 67% immune-restorative effect. The ethyl acetate fraction (EAF) maintained the most active fraction with significant (P < 0.05) antibody stimulatory effect in immunocompetent and immunosuppressed animals. Similarly, higher recovery rate was demonstrated by the EAF as shown by steep time recovery curve in high dose immunosuppressed animals. The EAF at 200 mg·kg?1 and 400 mg·kg?1 showed above 50% leucopoiesis just like the reference drug (2.5 mg·kg?1 levamisole), against 33.83% of leucopoiesis shown by the immune-suppressed control group. Conclusion: M. cecropioides boosted immune stimulation in immunocompetent animals and brought about fast rate of restoration of immune status in immunocompromised animals.