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Circadian rhythms play a major role in regulation of human physiological functions. Many signs and symptoms of inflammatory arthritis, especially in rheumatoid arthritis (RA), show intra- and inter-day variations. We aimed to measure serum levels of melatonin (MLT), interferon gamma (IFNγ), interleukin-10 (IL-10) and cortisol and to investigate relation with clinical parameters in patients with seronegative spondyloarthritis (SPA). The study was designed prospectively. 17 patients with SPA (9 patients with Anklyosing Sponylitis, 8 patients with psoriatic arthritis), 20 patients with RA and 20 healthy controls were included to study. Serum MLT, IFNγ, IL-10 and cortisol measurement were made in patients and healthy controls at 8 p.m., 3 a.m. and 8 a.m. We found that MLT values of SPA patients were statistically lower (p=0,017) than healthy groups at 3 a.m.. Level of cortisol in RA patients at 8 a.m. were significantly lower than SPA patient and healthy control groups (p=0.047 and p=0.006; respectively). Cortisol levels in SPA patients which is measured at 8 a.m. was significantly higher (p=0.001) than other measurement in day. There was also significant positive correlation between Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) and MLT levels measured at 8:00 p.m. in patients with SPA (r=0.688; p=0.040). Serum MLT levels well correlated with disease activity in SPA patients. Back pain which is seen midnight can be related to decrease in MLT secretion. Our findings suggests MLT have a role in pathogenesis of SPA but, it is need more detailed studies for explaining of this role of MLT in pathogenesis …