Abstract Background: Moderate hyperhomocysteinaemia related to folate deficiency has been described in patients with cardiovascular risk and also in patients with autoimmune diseases including rheumatoid arthritis (RA). Methods: In 33 patients with RA, serum concentrations of homocysteine and cysteine, of B-vitamins folate and vitamin B 12, and of immune activation markers neopterin and soluble 75-kDa TNF-receptor (sTNF-R75) were measured. Results: A significant proportion of patients presented with elevated homocysteine and cysteine concentrations in comparison to reference ranges of healthy control persons. Moderate hyperhomocysteinaemia coincided with decreased serum folate and with higher concentrations of sTNF-R75 and neopterin, but it was rather independent from methotrexate (MTX) therapy. Conclusions: The coincidence of higher homocysteine and lower folate concentrations with increased concentrations of immune activation markers in patients with RA suggests that immune activation could be involved in the development of hyperhomocysteinaemia.