To examine the relationship between disease activity and fatigue over time in early rheumatoid arthritis (RA). Data were from patients with early RA (duration of symptoms ≤12 months) enrolled in the Canadian Early Arthritis Cohort (CATCH). Patients rated their fatigue over the past week using an 11-point numerical rating scale (NRS) for up to 5 years of follow-up. Fatigue severity was classified as low (≤2), moderate (>2 but <5), or high (≥5). Differences in fatigue ratings in patients who achieved a low disease state (Disease Activity Score in 28 joints [DAS28] <3.2) and those who did not within 3-months of cohort entry were compared. Of 1,864 patients included, 88% met RA criteria, and 72% were women. The mean ± SD baseline DAS28 was 4.9 ± 1.5. Nineteen percent of the patients reported moderate baseline fatigue, and 59% reported severe baseline fatigue. Fatigue was correlated with pain and patient global ratings (r = 0.56-0.67, P < 0.001), and was weakly correlated with DAS28, tender joint count, swollen joint count, physician global assessment of disease activity, erythrocyte sedimentation rate, and C-reactive protein level. Patients who reported low fatigue by 3 months had significantly lower fatigue throughout follow-up compared to those who had moderate or high fatigue at 3 months (P < 0.001). Patients who achieved a DAS28 <3.2 within 3 months had significantly lower fatigue ratings (mean ± SD 2.7 ± 2.6) than those with a DAS28 >3.2 (4.6 ± 3.0) (P < 0.001), with improvements in fatigue that persisted through 5 years of follow-up. Maximal improvements in fatigue lagged behind remission by 6 months. Fatigue is common in early RA, and improvements may occur after remission. Early treatment response within 3-months was associated with short-term and long-term benefits in fatigue over time.