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Honey bees (Apis mellifera L.) are affected by different biotic and abiotic stressors, such as the fungus Nosema ceranae and neonicotinoid insecticides, that negatively impact their health. However, most studies so far conducted have focused on the effect of these stressors separately and in European honey bees. Therefore, this study was conducted to analyze the impact of both stressors, singly and in combination, on honey bees of African descent that have demonstrated resistance to parasites and pesticides. Africanized honey bees (AHBs, Apis mellifera scutellata Lepeletier) were inoculated with N. ceranae (1 × 105 spores/bee) and/or chronically exposed for 18 days to a sublethal dose of thiamethoxam (0.025 ng/bee) to evaluate their single and combined effects on food consumption, survivorship, N. ceranae infection, and immunity at the cellular and humoral levels. No significant effects by any of the stressors were found for food consumption. However, thiamethoxam was the main stressor associated to a significant decrease in AHB survivorship, whereas N. ceranae was the main stressor affecting their humoral immune response by upregulating the expression of the gene AmHym-1. Additionally, both stressors, separately and combined, significantly decreased the concentration of haemocytes in the haemolymph of the bees. These findings indicate that N. ceranae and thiamethoxam differentially affect the lifespan and immunity of AHBs and do not seem to have synergistic effects when AHBs are simultaneously exposed to both stressors.