The Baltic/Wadden Sea Flyway of common eiders has declined over the past three decades. Multiple factors such as contaminant exposure, global warming, hunting, white-tailed eagle predation, decreased agricultural eutrophication and infectious diseases have been suggested to explain the decline. We collected information on body mass, mercury (Hg) concentration, biochemistry and untargeted metabolomics of incubating birds in two colonies in the Danish Straits (Hov Røn, n = 100; Agersø, n = 29) and in one colony in the Baltic proper (Christiansø, n = 23) to look into their metabolisms and energy balance. Body mass was available from early and late incubation for Hov Røn and Christiansø, showing a significant decline (25–30%) in both colonies with late body mass at Christiansø being the lowest. Whole blood concentrations of total mercury Hg were significantly higher in birds at Christiansø in the east compared to Hov Røn in the west. All birds in the three colonies had Hg concentrations in the range of ≤1.0 μg/g ww, which indicates that the risk of effects on reproduction is in the no to low risk category for wild birds. Among the biochemical measures, glucose, fructosamine, amylase, albumin and protein decreased significantly from early to late incubation at Hov Røn and Christiansø, reflecting long-term fastening as supported by the decline in body mass. Untargeted metabolomics performed on Christiansø eiders revealed presence of 8,433 plasma metabolites. Of these, 3,179 metabolites changed significantly (log2-fold change ≥1, p ≤ 0.05) from the early to late incubation. For example, smaller peptides and vitamin B2 (riboflavin) were significantly down-regulated while 11-deoxycorticosterone and palmitoylcarnitine were significantly upregulated. These results show that cumulative stress including fasting during incubation affect the eiders’ biochemical profile and energy metabolism and that this may be most pronounced for the Christiansø colony in the Baltic proper. This amplify the events of temperature increases and food web changes caused by global warming that eventually accelerate the loss in body weight. Future studies should examine the relationship between body condition, temperature and reproductive outcomes and include mapping of food web contaminant, energy and nutrient content to better understand, manage and conserve the populations.