ABSTRACT Objectives: Of the world's 207 million estimated cases of Schistosomiasis, 93% occur in sub Saharan Africa (192 million) with Nigeria accounts for the largest number of registered cases. The pathogen S. haematobium carries glycoconjugates at all developmental stages that were demonstrated to interact with the lectin pathway proteins of the complement system. We investigated the possible association of the lectin proteins namely the Mannose binding lectin (MBL), Ficolins (FCN), Collectin-11 (CL-K1), and the downstream cleaving enzyme MBL associated serine protease 2 (MASP2) with Urinary Schistosomiasis in a Nigerian cohort. Methods: The individuals were recruited blindly irrespective of their infection status from southwest Nigeria (n=359). Based on their serology and egg counts in urine, the cohort was classified as Schistosoma Egg positive cases (SEP =168), Schistosoma ELISA positive controls (SELP=123) and Sero and Egg negative controls (SELN=68). The circulating serum levels of MBL, FCN, CL-K1 and MASP2 were measured by ELISA followed by subsequent genotyping of functional polymorphisms in the respective genes that were shown to alter the circulating serum levels and the binding affinity to the carbohydrate moieties in the pathogen. Results: Higher MBL, FCN and CL-K1 serum levels were associated with protection. MASP2 serum levels were differentially distributed among children and adults. The MBL2*HYPA haplotype, the FCN2 promoter variants (−986G>A and −4A>G), and the COLEC11*TCCA haplotypes were significantly associated with Schistosomiasis infection.