Technical Abstract: Managed honey bee colonies are currently affected by abrupt depopulation during winter and many factors are suspected to be involved, either alone or in combination. Pathogens are considered as principal actors, contributing to weaken colony health and leaving room for secondary infections. In particular, the ectoparasitic mite Varroa destructor is considered as the main candidate for these losses. This mite has been reported to have an impact on the bee immune system and to facilitate opportunistic infections. Indeed several harmful viruses are known to be vectored by Varroa destructor and this association is likely to enhance the deleterious action of mites on bee colonies. Another potential candidate involved in these losses is the microsporidian Nosema ceranae although its impact on colony health remains controversial. Despite the fact that several studies have pointed out the potential involvement of pathogens on colony losses, no common pattern has emerged. This is probably due in part to the different parameters present in these studies such as climate, bee races, beekeeping practices or sampling design. In this context long term monitoring appears crucial, especially because pathogens causing colony death may have disappeared leaving room for opportunistic infections. In this study, we identified four predictive markers of honeybee colony losses during winter out of eleven investigated among pathogens and genes involved in bee immunity and physiology: DWV, Nosema ceranae, Varroa destructor and Vitellogenin.