Abstract Background: Programmed cell death-1 (PD-1) is an immunoreceptor that negatively regulates antigen receptor signaling and plays a critical role in the immunoregulation of autoimmune diseases. Aim of the work: This study aimed to measure the plasma and synovial fluid levels of soluble programmed death-1(sPD-1) in rheumatoid arthritis (RA) patients and to correlate them with the clinical and laboratory characteristics, disease activity, functional status and radiological severity. Patients and methods: We measured sPD-1 in the plasma (n=60) and synovial fluid (SF) samples (n=24) from 60 RA patients and in the plasma from healthy control (n=30). In the patients, disease activity score using 28 joint counts (DAS28) and the health assessment questionnaire (HAQ) score were assessed; immunoglobulin-M rheumatoid factor (IgM-RF) titer, anti-cyclic citrullinated peptide (anti-CCP) antibodies titer and C-reactive protein (CRP) levels were measured and total Sharp score calculated. Results: In RA patients both plasma and SF sPD-1 levels (1416.9±1037.9 pg/ml and 1503.9±1129.48 pg/ml respectively) were highly significantly increased compared to its plasma level in the healthy control (165±26.11 pg/mL) (p