Small mammals in temperate areas face seasonal fluctuations of temperature and food availability, both of which may influence their immune responses, which are critical to survival. In the present study, we tested the hypothesis that low temperature and food restriction suppress immune function in striped hamsters (Cricetulus barabensis). Thirty-seven adult male hamsters were randomly assigned to warm (23±1°C) and cold (5±1°C) treatment groups, which were further divided into fed and food-restricted groups. Body mass was not affected by cold stress, food restriction or the interaction cold stress×food restriction. Cold stress decreased total body fat mass, haematological parameters including white blood cells, lymphocytes and neutrophilic granulocytes, and immunoglobin (Ig) M titres 5 days after injecting keyhole limpet haemocyanin (KLH). However, cold temperature increased bacterial killing capacity, indicative of innate immunity, and did not affect the mass of the thymus and spleen, intermediate granulocytes, the phytohaemagglutinin (PHA) response and the levels of blood glucose and serum leptin. Corticosterone concentration was affected significantly by the interaction cold stress×food restriction but not by cold stress or food restriction alone. Food restriction reduced thymus mass, but other immunological parameters including body fat mass, spleen mass, haematological parameters, innate immunity, PHA response, the titres of IgM and IgG, and the levels of blood glucose and serum leptin were all not affected by food restriction or the interaction cold stress×food restriction. Innate immunity was positively correlated with leptin levels, whereas no significant correlations were observed in the levels of blood glucose, serum leptin, corticosterone and all the detected immune parameters. Our results show that cold stress suppressed humoral immunity but enhanced innate immunity and did not affect cellular immunity in striped hamsters. Most immunological indices were not influenced by food restriction. Blood glucose, leptin and corticosterone could not explain the changes of innate, cellular and humoral immunity upon cold stress or food restriction in striped hamsters.