Although Culicoides sonorensis is an important vector of orbiviruses causing significant disease in domestic and wild ruminants in the USA, little is known about factors contributing to midge vector competence. In other vectors such as mosquitoes, interactions among the humoral immune response, microbiota, and ingested pathogens within the vector gut directly impact pathogen survival and therefore vectoring potential. We recently described components of the humoral immune response in the reference transcriptome for adult female C. sonorensis and analysed their temporal expression profiles across several dietary states (unfed, blood, or sugar fed). Blood feeding altered the transcription of several humoral immune components of the Immune deficiency (Imd), dual‑oxidase (DUOX), and Janus Kinase and Signal Transducer and Activator of Transcription (JAK/STAT) pathways. Genes for immune effectors, such as antimicrobial peptides, were in particular highly induced. Since blood feeding also stimulated proliferation and diversification of bacterial populations colonising the gut of female midges, we infer that changes in immune gene expression were a result of fluctuations in gut microbiota. Thus, diet can indirectly (via microbiota) impact gut immune status and therefore should be carefully considered in subsequent studies assessing vector competence in biting midges.