The blood biochemical characteristics and the activity of muscle ubiquitin-proteasome system of grass carp (Ctenopharyngodon idellus) infected with saprolegniasis were studied in the paper. 10 diseased and 10 healthy grass carps were randomly selected to collect serum and muscle samples. The serum biochemical indices were determined, including glucose (GLU), albumin (ALB), total protein (TP), cholesterol (CHO), triglyceride (TG), lactate dehydrogenase (LDH), alkaline phosphatase (ALP), aspartate aminotransferase (AST) and glutamic pyruvic transaminase (ALT). The mRNA expressions of nrf2, hsp70 and hsp90, and genes related to UPS as well as the content of ubiquitinated protein in fish muscles were investigated. The results showed that the concentrations of CHO, ALB, TP and TG in the serum of grass carp infected with saprolegniasis decreased significantly, while the activities of AST and LDH increased significantly. Compared with healthy grass carp, the mRNA expressions of nrf2, hsp70 and hsp90 in the muscle of diseased grass carp were significantly higher. The mRNA levels of chip, ub, psma2, psmc1, murf1 and mafbx in the muscles of grass carp with saprolegniasis were significantly up-regulated, as was the content of ubiquitinated protein. The results suggested that the saprolegniasis infection increased or decreased the serum biochemical indices, caused stress response and activated the ubiquitin-proteasome system of skeletal muscles in grass carp. The study can provide scientific references for the diagnosis and prevention of saprolegniasis. [Chinese Fishery Quality and Standards,2021,11(2):44-50]