Thyroid hormones (THs) are essential for cellular metabolism, somatic growth and development, and reproduction. Mercury (Hg) entering aquatic systems and accumulated as highly toxic methylmercury (MeHg) represents a threat to wildlife and human health. Selenium (Se) is an essential element critical for TH activation and regulation. In organisms, binding of Hg in a Se-Hg complex results in a detoxification of Hg. However, formation of Se-Hg complexes also affects Se bioavailability, disrupting functions of Se-dependent enzymes, such as TH deiodinases, which convert thyroxine (T4) to the physiologically active TH, triiodothyronine (T3). The main aim of the present study was to investigate how tissue Se:Hg molar ratios, tissue levels of Se and Hg, and other potential TH disruptive contaminants (metals and organic chemical compounds) affect plasma TH levels in free-ranging brown trout, Salmo trutta , from Lake Mjøsa (a Se-deprived lake) and Lake Losna (a reference lake), Norway. Among the wide range of potential TH disruptive pollutants investigated, tissue Se:Hg molar ratios in muscle and liver were the most significant predictors of plasma TH levels in the trout. Moreover, lower plasma levels of the biological active hormone, T3, in the Lake Mjøsa trout co-occurred with their low Se:Hg molar ratios. This suggests that Se availability is impaired by Hg and results in altered selenoenzyme activities and loss of optimal control of TH balance in free-ranging freshwater fish.