The host response to helminth infections is characterized by systemic and tissue-related immune responses that play a crucial role in pathological diseases. Recently, experimental studies have highlighted the role of regulatory T (Tregs) and B (Bregs) cells with secreted cytokines as important markers in anti-schistosomiasis immunity. We investigated the serical levels of five cytokines (TNFα, IFN-γ, IL-4, IL-10 and IL-35) in pre- and post-treatment samples from chronicSchistosomainfected patients to identify potential serological markers during follow-up therapy. Interestingly, we highlighted an increased serum level of IL-35 in the pre-therapy samples (median 439 pg/mL forSchistosoma haematobiumand 100.5 pg/mL forSchistsoma mansoniinfected patients) compared to a control group (median 62 pg/mL and 58 pg/mL, respectively,p≤ 0.05), and a significantly lower concentration in post-therapy samples (181 pg/mL forS. haematobiumand 49.5 pg/mL forS. mansoniinfected patients,p≤ 0.05). The present study suggests the possible role of IL-35 as a novel serological biomarker in the evaluation ofSchistosomatherapy follow-up.