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The albumin to fibrinogen ratio (AFR) and C-reactive protein to albumin ratio (CAR) have emerged as useful biomarkers to predict systemic inflammation. The aim here is to investigate the relation between AFR/CAR and Disease Activity Score of 28 joints (DAS 28) in rheumatoid arthritis (RA).This retrospective study included 160 patients with RA and 159 healthy controls. We divided the RA patients into two groups according to the DAS 28-ESR score. Group 1 included 40 patients with a score of lower than 2.6 (patients in remission) and Group 2 included 120 patients with a score of 2.6 or higher (patients with active disease). The correlations between AFR, CAR and the disease activity were analyzed.For RA patients, the AFR was lower than those in the control group (P < 0.001). Patients in group 2 had higher CAR than those in group 1 (P < 0.001). The AFR was lower in group 2 than that in group 1. A positively correlation was observed between DAS 28-ESR score and CAR (r = 0.645, P < 0.001), while the correlation between DAS 28-ESR and AFR (r = −0.836, P < 0.001) was negative. AFR was related with decreased risk of RA disease activity (EXP (B) = 0.33, 95% CI (0.21–0.53), P < 0.001).AFR and CAR are two novel inflammatory markers for monitoring disease activity in patients with RA.AFR were lower and CAR were higher in RA patients with active disease.AFR and CAR were significantly correlated with NLR, PLR, CRP and ESR in RA patients.AFR was related with decreased risk of RA disease activity.AFR and CAR were novel inflammatory markers for diagnosing RA disease activity.