The aim of this study was to assess fatigue aspects in Moroccan patients with rheumatoid arthritis (RA) and its relationships with disease-specific variables especially parameters of functional and structural severity. A total of 248 patients with RA were included. Patients' and disease characteristics were identified. Disease activity was measured clinically using physical examination, biologically and by the disease activity scores (DAS28). Radiographs were evaluated by using Sharp's method as modified by van der Heijde. Functional disability was measured by using the Moroccan version of Health Assessment Questionnaire (HAQ). Immunological abnormalities and treatment (doses and duration) were identified. Fatigue was evaluated by using a 0-100 visual analogue scale (VAS fatigue) and the multidimensional assessment of fatigue (MAF). Quality of life (QoL) was assessed using the Arabic version of the generic instrument SF-36. The mean age of patients was 47.5 ± 11.7 years [25-72]; 37.5% of patients had a high activity of disease and 11.3% were in remission. The mean Sharp score was 107.13 ± 91, and the mean score of HAQ was 1.40 ± 0.63. All domains of QoL were deteriorated; 89.51% of our patients experienced fatigue. The mean total score of MAF was 30.21 ± 11.32. A low level of education, low socioeconomic status, atlantoaxial subluxation, hip involvement, the presence of a Sjögren syndrome, and cigarette smoking had a negative impact on fatigue scores. The severity of fatigue was correlated with the duration of RA, the intensity of joint pain, the activity of disease, the importance of structural damage, the degree of functional impairment, and the rate of anti-cyclic citrullinated protein (CCP) antibodies (P < 0.05). Patients receiving methotrexate had better scores of fatigue. Also, severity of fatigue was correlated with the deterioration of all domains of QoL. Fatigue is a major issue for our patients with RA and must be included in the routine assessment of patients. In our sample, fatigue appears to be related to disease activity, functional disability, structural damage, and immunological status and had a negative impact on QoL.