Pesticide application can have an adverse effect on pollinator honey bees,Apis melliferaL., ranging from mortality to sublethal effects. Therefore, it is necessary to understand any potential effects of pesticides. The present study reports the acute toxicity and adverse effects of sulfoxaflor insecticide on the biochemical activity and histological changes onA. mellifera. The results showed that after 48 h post-treatment, the LD25and LD50values were 0.078 and 0.162 µg/bee, respectively, of sulfoxaflor onA. mellifera. The detoxification enzyme activity shows an increase of glutathione-S-transferase (GST) enzyme onA. melliferain response to sulfoxaflor at LD50value. Conversely, no significant differences were found in mixed-function oxidation (MFO) activity. In addition, after 4 h of sulfoxaflor exposure, the brains of treated bees showed nuclear pyknosis and degeneration in some cells, which evolved to mushroom shaped tissue losses, mainly neurons replaced by vacuoles after 48 h. There was a slight effect on secretory vesicles in the hypopharyngeal gland after 4 h of exposure. After 48 h, the vacuolar cytoplasm and basophilic pyknotic nuclei were lost in the atrophied acini. After exposure to sulfoxaflor, the midgut ofA. melliferaworkers showed histological changes in epithelial cells. These findings of the present study showed that sulfoxaflor could have an adverse effect onA. mellifera.