Honeybee colony mortalities have been too high for more than two decades. This threatens not only honeybees and wild bees but also our own well-being as honeybees are important pollinators in both natural and agricultural ecosystems. Honeybees are dying due to a disease complex caused by uncertain combinations of pesticides, pathogens and nutritional deficiencies. Currently, there are no satisfying treatments for this syndrome. The used chemicals can be dangerous for bees and humans and genetic selection has only a limited effect due to the absence of definite markers. We propose a spatio-temporal follow-up of honeybee parameters (detection of parasites, viruses and bacteria, hemocyte profiling by cytospin stainings and flow cytometry (with the use of monoclonal antibodies), histological analysis of barriers and identifying of the gut microbiome) and environmental stressors (pesticides) at a high frequency. The virological and bacteriological analysis will be performed by third-generation nanopore sequencing which has already been proven vital to identify new players in disease complexes. Stressors that will be associated with honeybee mortality will be used to perform experimental exposures. Disease reproduction with one stressor or a combination of stressors will confirm that the stressor(s) is(are) a causative agent(s). At the end, concrete measures will be developed/implemented to prevent future hive mortality.