The European honey bee (Apis mellifera) is confronting several environmental challenges, including the intermingled effects of malnutrition and pesticide exposure. Pollen is intuitively the healthiest choice for honey bee nutrition, but despite their unclear nutritional value, commercial pollen substitutes are widely used to offset pollen shortages. In this study, we subjected honey bee to a harmful dose of a mixture of the pesticides chlorpyrifos and fluvalinate and examined if the bee response to chemical detriment is impacted by diet quality. Newly emerging bees were distributed into 3 groups of 6 cages, with each group receiving one of the following diets: pollen / sucrose, MegaBee / sucrose or sucrose only. On day-5, for each diet, 3 cages were kept pesticide-free to constitute the controls while, for 5 consecutive days, the remaining cages were fed a chlorpyrifos / fluvalinate mixture to constitute the chemically compromised treatment. For all groups, at day-10 of the experiment, several physiological traits (body weight, whole body protein content, midgut proteolytic enzyme activity, hindgut protein content, and total protein digested) were measured. We also examined the transcription levels of nutrition response genes, primary and secondary antioxidants, detoxification genes, immunity genes as well as acetylcholinesterase (AChE) which is the target of the organophosphate Chlorpyrifos.