Bees, including solitary and social, native and managed, are vital insect pollinators that provide essential ecosystem services. Bombus terrestris (Linnaeus) is a widespread and important bumblebee pollinator of wild and cultivated crops and although found commonly across Europe, is available commercially to supplement pollination requirements. Due to their activity, B. terrestris workers encounter a variety of diseases which in addition to habitat loss and agrichemical use, are key factors in global bumblebee declines. The profound economic and environmental consequences of this decline warrant a detailed investigation of the molecular and cellular aspects of bumblebee health. The principal components of the B. terrestris immune system, the fat body (FB) and haemolymph were characterised here using proteomic and cytological methodologies. The FB proteome is highly enriched in metabolic, detoxification and proteostasis processes whereas the haemolymph is enriched in cellular transport and immunity. At a cellular level the FB was shown to predominantly comprise adipocytes and oenocytes, while spherulocytes, oenocytoids and plasmatocytes were the most frequently found haemocytes in bumblebee haemolymph. The FB and haemolymph were also investigated under various stresses and contexts. In general, typical immune responses to microbial challenge were observed although immune signatures were lower than expected. Although specific responses to Gram-positive and Gram-negative bacteria and fungi were observed, a broad and conserved response to microbial challenge was found. The major responses in both the haemolymph and FB, however involved energy metabolism, protein processing and detoxification which provides insight into the mechanisms that support and regulate the immune response in bumblebees. Worryingly, pesticide exposure had a significant effect on the FB proteome and its ability to mount an immune response. Overall these results provide novel insights into molecular aspects of bee health and highlight the importance of nutrition and the risks posed by pesticides use on our important pollinator species.