Sodium butyrate is commonly used in mammalian cell cultures to increase the productivity of recombinant proteins. A Chinese hamster ovary (CHO) cell line producing recombinant human erythropoietin (rhEPO) was cultured in commercial medium. Addition of 0.5 mM butyrate inhibited the over-growth of the cells after the medium was changed from serum-added medium to serum-free medium. At the 6th day, the addition of butyrate lowered the transcriptional level of sialidases I, II, and III compared to that of control groups by 56, 87, and 59 %, respectively. Extracellular sialidase activity was decreased by 53 % by addition of butyrate. The inhibition of cell over-growth and the decrease of extracellular sialidase activity helped to increase the acidic isoform content of rhEPO expressed by this CHO cell strain.