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Background: Being a parent can be demanding and stressful, especially for people with chronic diseases such as multiple sclerosis (MS). Parenting can be disrupted by flareups, disease worsening, and other MS symptoms, including mobility problems, pain, fatigue, and cognitive impairment. Mood disorders, such as depression and anxiety, have been found to occur at much higher rates in people with MS than in the general population. Surprisingly, less is known about which factors may predict mood disorders in parents with MS. This study aims to identify potential demographic, clinical, and self-reported predictors that contribute to mood disorders measured by the Hospital Anxiety and Depression Scale., Methods: A total of 285 parents with MS completed an anonymous online questionnaire combining sociodemographic, clinical, and family characteristics and scales, validated in Italian, related to coping strategies and social support. Associations between each variable and mood disorders were assessed using univariate and multivariate logistic regression analyses., Results: Disability level, emotional and dysfunctional coping strategies, and perceived social support were significant predictors of mood disorders in parents with MS., Conclusions: These findings confirm the importance of identifying risk factors for mood disorders in parents with MS so that early intervention can minimize mood disruptions caused by the disease., Competing Interests: FINANCIAL DISCLOSURE: Ms Messmer Uccelli is currently employed by Biogen. The other authors have disclosed no relevant financial relationships., (© 2022 Consortium of Multiple Sclerosis Centers.)