To evaluate the changes in lysosomal enzyme activities in leukocytes of patients with Sjögren’s syndrome.Leukocytes were obtained from 38 patients with Sjögren’s syndrome and 36 healthy subjects. The activities of the following glycosidases were measured: α-glucosidase (AGU), β-galactosidase (BGA), α-mannosidase (AMAN), β-glucuronidase (GCU), β-hexosaminidase (HEX), and the following proteases: cathepsin B (CATH B), dipeptidyl peptidase I (DPP I), cathepsin H (CATH H), dipeptidyl peptidase II (DPP II), tripeptidyl peptidase I (TPP I), and cathepsin D (CATH D) activity.Activity of the glycosidases β-galactosidase, α-mannosidase, β-glucuronidase and β-hexosaminidase, as well as of the peptidases cathepsin B, cathepsin D, dipeptidyl peptidase I, and tripeptidyl peptidase I, was elevated during the first 5 years of SS, and it increased further between 5 and 10 years after diagnosis.The elevated activities of the lysosomal enzymes in Sjögren’s syndrome patients may play a role in tissue damage by accelerated breakdown of glycoproteins in lysosomes.