Human ficolin 2 (encoded by FCN2) and mannose-binding lectin (encoded by MBL2) bind to specific pathogen-associated molecular patterns, activate the complement lectin cascade in a similar manner, and are associated with several infectious diseases. Our recently published study established certain FCN2 promoter variants and ficolin-2 serum levels as protective factors against schistosomiasis.We used the Nigerian cohort from our recently published study, which included 163 Schistosoma haematobium-infected individuals and 183 matched healthy subjects, and investigated whether MBL deficiency and MBL2 polymorphisms are associated with schistosomiasis.MBL serum levels were significantly higher in controls and were associated with protection (P < .0001). The -550H minor allele was significantly associated with protection (P = .03), and the heterozygous genotypes -550HL were observed to confer protection (P = .03). The MBL2*HYPA haplotype was significantly associated with protection (P = .03), with significantly higher serum MBL levels in controls (P = .00073). The heterozygous 6-bp deletion in the promoter was observed to be a susceptibility factor in schistosomiasis (P = .03).In agreement with findings from our recently published study, the findings reported here support the observation that MBL is also associated with protection in schistosomiasis.