Forty two Djallonké and 27 Djallonké-Sahelian crossbred sheep were compared during 34 weeks for their disease resistance and productivity in a multifactorial experiment including trypanosome infection, helminth infections and dietary level. Eight treatment combinations were formed in which the two breeds were balanced. Pyrexia was observed following trypanosome infection and was not different between the two breeds. However, a significant higher parasitaemia level, a shorter prepatent period and a lower antibody response in the crossbreds following infection, indicated a significant reduction of the trypanotolerance and confirmed the genetic origin of the trait. Neither helminth infection nor dietary level influenced the onset and level of parasitaemia or the level of antibody response following trypanosome infection. Trypanosome infection, helminth infection and low supplementary feeding caused independently significant reductions in PCV level and weight gain but these declines were not worse in crossbreds as compared to Djallonké. Independently, of the studied factors, crossbreds were generally heavier than Djallonké and also grew faster, especially during the second phase of the study. Crossbreds had significantly higher mean nematode egg output (epg) compared to Djallonké sheep but reduction of epg following deworming was similar in both breeds. The lower epg in the Djallonké breed indicated an innate resistance to helminths and/or more efficient immune response. Trypanosome infection tended to increase epg, confirming the immunosuppressive effect of the former. The higher body temperature in the Djallonké compared to crossbreds suggested a better heat tolerance in the former breed. From this study it was concluded that Djallonké-Sahelian crossbred sheep inspite of a reduced trypanotolerance and lower resistance to helminth infection, posses a higher potential to intensify mutton production as compared to the pure Djallonké. However, appropriate measures should be taken to limit disease and stress factors in order to optimise production environment for this crossbred sheep.