Pesticide usage associated with intensive agriculture is implicated as a major factor for pollinator decline. Apart from developmental and physiological impairments, pesticide exposure has been shown to cause major cognitive anomalies in honey bees. However, there are gaps in our understanding about the physiological and molecular mechanism that causes the impairments. The present study evaluates the tissue damages at the molecular level with focus on apoptosis in the wild population of honey bees exposed to pesticide cocktails corroborated by observations in laboratory experiments. The study, for the first time, reports increase in both mitochondria and endoplasmic reticulum-mediated apoptosis in the honeybee body tissues underpinned by significant oxidative stress leading to programmed cell death. There was heightened reactive oxygen species level and caspase3 activity in the tissue homogenates from bees exposed to pesticides. Western blot experiments showed a significant increase in the expressions of the apoptotic markers like p53, cytochrome C, and GADD153/CHOP (DNA damage 153 or C/EBP homologous protein) in the pesticide-exposed bee populations in both field and laboratory conditions. Expressions of these apoptotic markers and oxidative stress were more pronounced in the heads as compared to the abdomens of the pesticide-exposed bees. These findings clearly indicate greater tissue damage in the honeybee head tissue. The cognitive implication of this finding has been discussed.Graphical abstract