We evaluated the roles of sociocultural status, distress and cognitive functions in rheumatoid arthritis (RA) patients who developed methotrexate (MTX)-related neutropenia. The data of 37 RA patients with MTX-related neutropenia who were being followed up at 3 centers were evaluated. The control group included 74 RA patients. The clinical features, biochemical tests and treatment modalities of the patients were obtained from hospital files. The mini-mental state examination (MMSE) test and the Hospital Anxiety and Depression Scale (HADS) were administered for all RA patients with neutropenia as well as the control group. The frequencies of male patients, illiterate patients, patients living alone, patients with serious visual impairment, those with low income, and patients with high creatinine were significantly higher among RA patients with MTX-related neutropenia than in controls (p values < 0.05). The RA patients with MTX-related neutropenia had significantly lower MMSE scores, and significantly higher HADS-A and HADS-D scores than controls (p values < 0.05). In addition, the proportion of patients with probable dementia was significantly higher in RA patients with MTX-related neutropenia than in controls (p < 0.001). Twenty-six of the 37 patients (70.3 %) developed neutropenia with daily dosing. Patients who used MTX daily were more likely to be living alone than those using weekly dosing (p = 0.011). Multivariate analysis showed that having probable dementia on the MMSE test (OR 52.6), low income level (OR 56.8) and age (OR 1.12) were independent risk factors for the development of MTX-related neutropenia. The presence of probable dementia on MMSE, low socioeconomical status and older age are associated with serious toxicity in RA patients using MTX. Measures should be taken to prevent wrong MTX dosing by the patients. Compliance and patient education is of major importance, in particular, in the patients presented in this study.