In areas endemic for schistosomiasis, people can often be in contact with contaminated water resulting in repeated exposures to infective Schistosoma mansoni cercariae. Using a murine model, repeated infections result in IL-10-dependent CD4+ T-cell hyporesponsiveness in the skin-draining lymph nodes (sdLN), which could be caused by an abundance of eosinophils and connective tissue mast cells at the skin infection site. Here, we show that whilst the absence of eosinophils did not have a significant effect on cytokine production, MHC-II+ cells were more numerous in the dermal cell exudate population. Nevertheless, the absence of dermal eosinophils did not lead to an increase in the responsiveness of CD4+ T cells in the sdLN, revealing that eosinophils in repeatedly exposed skin did not impact on the development of CD4+ T-cell hyporesponsiveness. On the other hand, the absence of connective tissue mast cells led to a reduction in dermal IL-10 and to an increase in the number of MHC-II+ cells infiltrating the skin. There was also a small but significant alleviation of hyporesponsiveness in the sdLN, suggesting that mast cells may have a role in regulating immune responses after repeated exposures of the skin to S. mansoni cercariae.