The authors of this study assessed the physical and mental quality of life (QoL) in 62 adult patients with spinal muscular atrophy (SMA), with the aim of improving care for patients with SMA. Physical component scores (PCS) and mental component scores (MCS) of the Short Form -36 Health Survey (SF-36) were obtained. Correlations with demographics, disease severity, and emotional distress were assessed. Hierarchical multiple regression analysis was used to identify determinants of QoL. PCS scores were lower, and MCS scores higher than in the healthy reference population. Patients with milder SMA types reported lower scores on several MCS domains. Motor skills scores and emotional distress explained 16% of the variance in PCS. SMA type and emotional distress explained 10% and 45% of the variance of MCS. Patients with milder forms of SMA tend to have a reduced mental QoL. Psychological intervention to reduce emotional distress may improve both mental and physical QoL.