The adaptive evolution of the Notothenia rossii occurred under the selective pressure of stable and low temperatures. It is an opportunistic feeder of Antarctic krill and the fluoride in the krill carapace is apparently not toxic. We investigated the interactive effect of fluoride, elevated temperatures, and low salinity on the plasmatic constituents of this Antarctic fish. The experiments were conducted at the Brazilian Antarctic Station Comandante Ferraz (EACF), located on King George Island. The Antarctic fish N. rossii was acclimatized to eight thermo-saline-trophic conditions, combining two temperatures (0 and 4 °C), two salinities (35 and 20), and two trophic conditions (with/without fluoride) for an 11-day period. Trophic fluoride was not able to alter the plasmatic levels of glucose, cholesterol, plasmatic protein, Cl⁻, Mg²⁺, Ca²⁺, and inorganic phosphate, but induced an acute elevation of triglycerides at 0 °C and salinity of 35. At low salinity, hyperglycemia, hypertriglyceridemia, and hypocalcemia were observed. The thermo-saline interaction at 4 °C was able to minimize the effects of fluoride and low salinity on the plasmatic constituents levels.