Summary The aim of this study was to investigate the cross‐resistance between Fasciola hepatica and Schistosoma bovis in lambs assessing parasitologic, gross pathologic, histopathologic and immunohistochemical changes in liver and small intestine. Thirty Castellana breed lambs were divided into five comparable groups and exposed to F. hepatica/S. bovis (group F/S), S. bovis/F. hepatica (group S/F), S. bovis (group S) or F. hepatica (group F) and six unexposed lambs were used as non‐infected controls (group C). Primary patent infection with F. hepatica induced a lower number of schistosome eggs and a higher number of lymphocytes in intestinal and liver schistosome egg‐induced granulomas in group F/S than in the groups S/F and S, liver damage being mainly attributed to F. hepatica. S. bovis infection followed by challenge with F. hepatica particularly increased the severity of the most significant liver alterations (cholangiohepatitis by F. hepatica and mesoendophlebitis by S. bovis) and F. hepatica seemed not to have an influence on established S. bovis infection. In addition, immunohistochemical results suggested that the predominant local immune response in both double‐infected groups was different, being mainly a cell‐mediated immune response in group F/S and a mucosal response in group S/F.