Experimental schistosome infections induce strong parasite‐specific Th2 responses. This study aims to relate human systemic cytokine and antibody levels to schistosome infection levels and history. Levels of anti‐Schistosoma haematobium antibodies (directed against crude cercariae, egg and adult worm antigens) and plasma cytokines (IFN‐γ, IL‐2, IL‐4, IL‐5, IL‐10, IL‐13, IL‐17, IL‐21, and IL‐23) were measured by ELISA in 227 Zimbabweans (6–60 years old) in a schistosome‐endemic area and related to age and infection status. Egg‐positive people had significantly higher levels of specific antibodies, IL‐2, IFN‐γ and IL‐23. In contrast, egg‐negative individuals had significantly higher circulating IL‐10, IL‐4, IL‐13 and IL‐21 that were detected with high frequency in all participants. Subjects with detectable plasma IL‐17 produced few or no eggs. When analyzed by age, IL‐4 and IL‐10 increased significantly, as did schistosome‐specific antibodies. However, when age was combined with infection status, IL‐5 declined over time in egg‐positive people, while increased with age in the egg‐negative group. Older, lifelong residents had significantly higher IL‐4 and IL‐5 levels than younger egg‐negative people. Thus, a mixed Th1/Th2 systemic environment occurs in people with patent schistosome infection, while a stronger Th2‐dominated suite of cytokines is evident in egg‐negative individuals.