Honeybees are exposed during their foraging activities to a large variety of pollutants including pesticides. Overwintered honeybees are, as a result, subjected to chronic sublethal exposures of pesticide mixtures. To explore the impact of different pesticide combinations on winter honeybee survival, we chronically exposed adult overwintered honeybees during 16 days to low concentrations (0.01, 0.1, 1 and 10 μg/L) of imidacloprid (neonicotinoid insecticide), difenoconazole (triazole fungicide) and glyphosate (amino-phosphonate glycine herbicide) alone or in binary and ternary mixtures. The survival rates and food consumption were recorded daily. In order to measure the impact on oxidative balance, we measured the activity of six enzymes involved in the antioxidative defenses in the honeybee’s head, midgut and abdomen and oxidative stress damages by quantifying midgut lipid and protein oxidation accompanied with midgut histological analysis. Mortality rates suggest that the effects on bees are not dose dependent; the concentration of 0.1 μg/L induces the highest mortality rates, followed by the concentrations of 1 and 10 μg/L. In addition, pesticide mixtures have higher impact than pesticides alone. These effectsvary according to the combinations and the concentrations: An additive effect was observed with the insecticide-fungicide mixture at the 4 different concentrations and at 1 and 10 μg/L for the ternary mixture, whereas a synergistic effect occurs with the ternary mixture at 0.1 μg/L and the insecticide-herbicide mixture at 0.01, 1 and 10 μg/L. The physiological markers, and the lipid and protein oxidation, reveal a disruption of oxidative balance at 1 μg/L with an increase of the activities of glutathione-S-transferase, glutathione reductase and glutathione peroxidase in the head, and superoxide dismutase, glucose-6-phosphate dehydrogenase and glutathione-S-transferase in the midgut. Conversely, a decrease is observed for superoxide dismutase in the head and catalase in the midgut. These results suggest that these three types of agrochemicals with different mode of actions may have common molecular targets in honeybees, leading, when combined, to greater alterations and drastic honeybee mortality.