The aim of this report was to evaluate the morphological and biochemical changes in the liver by the inhalation of vanadium and consumption of sweetened beverages in a subchronic murine model. Forty CD-1 male mice were randomly divided into four groups: control, vanadium (V), sucrose 30% (S), and vanadium–sucrose (V + S). V was inhaled (1.4 mg/m3) for 1h, twice/week; 30% sucrose solution was given orally ad libitum. Blood samples were obtained for AST, ALT, and LDH determination. Liver samples were processed for histological and oxidative stress immunohistochemical evaluation with 4-hydroxynonenal at weeks 4 and 8 of exposure. Regarding liver function tests, a statistically significant increase ( P < 0.05) was observed in groups V, S, and V + S at weeks 4 and 8 compared to the control group. A greater number of hepatocytes with meganuclei and binuclei were observed in V and V + S at week 8 compared to the other groups. Steatosis and regenerative changes were more extensive in the eighth week V + S group. 4-Hydroxynonenal immunoreactivity increased in the V + S group at both exposure times compared to the other groups; however, the increment was more evident in the V + S group at week 4 compared to the V + S group at week 8. An increase in De Ritis ratio (>1) was noticed in experimental groups at weeks 4 and 8. Findings demonstrate that in the liver, V, S, and V + S induced oxidative stress and regenerative changes that increased with the length of exposure. Results support possible potentiation of liver damage in areas with high air pollution and high-sweetened beverage consumption.