We investigated activities of glutathione peroxidase (GSH-Px), glutathione reductase (GR), and the phase II biotransformation enzyme glutathione-S-transferase (GST) in the foot of three freshwater mussel species: Unio pictorum (Up), Unio tumidus (Ut), and Sinanodonta woodiana (Sw) from the Sava River. Specific and total GSH-Px activity was lower in Sw than in Up and Ut. Total GR activity was higher in Up than in Sw. Specific GST activity was higher in Up than in Ut. Total GST activity was higher in Up than in Ut and Sw. Electrophoretic analysis of proteins shows species specifities between the investigated mussel species. Our study represents the first comprehensive report of the investigated glutathione-dependent enzyme activities in the foot of three freshwater mussel species from the Sava River, Serbia. .