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Simple Summary: The collapse of the honey bee colonies is a complex phenomenon in which different factors may participate in an interrelated manner (e.g., pathogen interactions, exposure to chemicals, beekeeping practices, climatology, etc.). In light of the current debate regarding the interpretation of field and monitoring studies in prospective risk assessments, here we studied how exposure to thiamethoxam affects honey bee colonies in Central Spain when applied as a seed treatment to winter oilseed rape, according to the good agricultural practice in place prior to the EU restrictions. Under the experimental conditions, exposure to thiamethoxam, alone or in combination with other stressors, did not generate and maintain sufficient chronic stress as to provoke honey bee colony collapse. The stress derived from exposure to thiamethoxam and honey bee pathogens was compensated by adjustments in the colony's dynamics, and by an increase in the worker bee population, a behavior known as hormesis. An analysis of the factors underlying this phenomenon should be incorporated into the prospective risk assessment of plant protection products in order to improve the future interpretation of field studies and management practices. To study the influence of thiamethoxam exposure on colony strength and pathogen prevalence, an apiary (5 colonies) was placed in front of a plot sown with winter oilseed rape (wOSR), just before the flowering phase. Before sowing, the seeds were treated with an equivalent application of 18 g thiamethoxam/ha. For comparison, a second apiary (5 colonies) was located in front of a separate 750 m plot sown with untreated wOSR. Dead foragers at the entrance of hives were assessed every 2–3 days throughout the exposure period, while the colony strength (number of combs covered with adult honey bees and brood) and pathogens were monitored each month until the following spring. Foraging on the wOSR crop was confirmed by melissopalynology determination of the corbicular pollen collected periodically, while the chemical analysis showed that exposure to thiamethoxam was mainly through nectar. There was an increase in the accumulation of dead bees in the apiary exposed to thiamethoxam relating with the control, which was coped with an increment of bee brood surface and adult bee population. However, we did not find statistically significant differences between apiaries (α = 0.05) in terms of the evolution of pathogens. We discuss these results under hormesis perspective. [ABSTRACT FROM AUTHOR]