Background There are limited data regarding the contribution of advanced glycation end products in the presence of rheumatoid arthritis. We investigated whether serum Nɛ-carboxymethyllysine and pentosidine were related to the presence and the severity of rheumatoid arthritis. Methods Eighty patients with rheumatoid arthritis and 30 control subjects were included in a cross-sectional study. The severity of rheumatoid arthritis was assessed using the disease activity score for 28 joints. Serum Nɛ-carboxymethyllysine and pentosidine were measured by enzyme-linked immunosorbent assay. Results Serum Nɛ-carboxymethyllysine and pentosidine concentrations were significantly higher in patients with rheumatoid arthritis vs. control subjects ( P < 0.001). Serum Nɛ-carboxymethyllysine and pentosidine concentrations were significantly higher in rheumatoid arthritis patients with high disease activity vs. rheumatoid arthritis patients with moderate disease activity ( P < 0.001, P = 0.019, respectively). A multiple logistic regression analysis demonstrated that Nɛ-carboxymethyllysine was independently associated with the presence of rheumatoid arthritis (OR = 1.21, 95% CI: 1.05-1.39, P = 0.006). Furthermore, in a multivariate stepwise regression analysis, Nɛ-carboxymethyllysine was independently correlated with disease activity score for 28 joints (standardized β = 0.43, P = 0.001). Conclusion Serum Nɛ-carboxymethyllysine and pentosidine were increased during rheumatoid arthritis, and Nɛ-carboxymethyllysine was independently associated with the presence and the severity of rheumatoid arthritis.