Domains encompassing emotional disorders in relapsing-remitting MS (RRMS) patients are still unclear. We performed a 24-month, multicenter, single-arm, prospective study. RRMS patients started IFN-β treatment at baseline. The primary endpoint was lack of emotional control, measured using the “Echelle d'HumeurDépressive” (EHD) scale three times at baseline and at 10 post-treatment visits. Secondary endpoints were emotional blunting, irritability, fatigue, depression and anxiety. A linear mixed covariance model assessed change from baseline on an intention-to-treat basis, under the assumption of no mood disorder effect (one-sided 97.5% level), in which autoregressive type of autocorrelation was tested. Out of 79 recruited patients, 70 were analyzed: 80% female; mean (SD) age, 37.0 (11.5) years. Mean (SD) lack of emotional control score at baseline and Month 24 was 12.7 (4.4) and 12.6 (5.5), respectively, versus 10.1 (3.2) in a healthy control population matched for age and sex. Stepwise analysis identified younger age, male sex and antidepressant use as significant predictors of higher lack of emotional control values. Based on 24 months of prospective follow-up, the results of this study highlights a broad spectrum of emotional disorders in the MS population at the time of disease modifying drugs initiation but no major IFN-β-related emotional disorders (mood dyscontrol, anxiety, depression) were observed. However, sporadic occurrences of severe mood disorders and suicidality cannot be excluded. •70 MS patients including 16 evaluations•This 24-month prospective study identifies emotional disorders in MS patients.•On an intent-to-treat basis no significant change under interferon-β treatment.•Sporadic emotional disorders under interferon-β treatment cannot be excluded.