Objective: In patients with rheumatoid arthritis (RA), the relation between fatigue and disease activity is not established, and our objective was to explore in post hoc analyses the associations between fatigue and subjective as well as objective assessments of inflammation during follow-up of patients with RA initiating biologic treatment. Methods: In a Nordic multicenter study, patients with RA starting tocilizumab were examined for fatigue (Functional Assessment of Chronic Illness Therapy–Fatigue sum score) as well as patient-reported outcome measures (PROMs) (patient's global disease activity, joint pain, and Health Assessment Questionnaire Disability Index), clinical examinations (examiner's global disease activity, 28 tender/swollen joint counts), laboratory variables (erythrocyte sedimentation rate, C-reactive protein), and ultrasound assessments (semiquantitative scoring [0-3]) of gray scale and Doppler of 36 joints and 4 tendons) at baseline and 4, 12, and 24 weeks. The associations were explored by using nonparametric tests, including the Wilcoxon rank test, the Mann–Whitney U test, Spearman correlations, and a linear regression and linear mixed model. Results: One hundred ten patients were included (83% female, mean [SD] age 55.6 [12.1] years, mean [SD] RA duration 8.7 [9.5] years, 81% anti–cyclic citrullinated peptide positive). Fatigue, PROMs, and clinical, laboratory, and ultrasound variables all decreased significantly during follow-up, already at 4 weeks (P < 0.001). Fatigue was both cross-sectionally and longitudinally associated with PROMs, whereas there were no or low associations with clinical, laboratory, or ultrasound assessments of inflammation. Baseline fatigue was predictive of PROMs at 12 and 24 weeks (P < 0.05 and P < 0.001, respectively) but not of any objective assessments. Conclusion: Fatigue was primarily associated with subjective assessments of disease activity. Thus, the present study supports fatigue to reflect other aspects of RA disease activity than inflammation.