BackgroundIndicators of emotional processes (positive experiences with physical exercises) and functional processes (mobility) were previously found to be associated with positive cognitive resources (meaning in life), and the key outcome in the rehabilitation, namely physical quality of life (QOL). Yet, the mediating roles of such processes were not tested. Therefore, this prospective study investigated whether the relationship between meaning in life and physical QOL was mediated by positive experiences with physical exercises and mobility.MethodsProspective data were collected at two measurement points, 1 month apart. A total of N = 339 participants (aged 19–84 years old, 57.9% women) provided data at Time 1 (T1) at the beginning of inpatient rehabilitation from central nervous system diseases (CNSD, e.g., stroke; n = 89) or musculoskeletal system diseases (MSD, e.g., dorsopathies; n = 250), and n = 234 at Time 2 (T2, the end of rehabilitation; 4 weeks after T1). Mediation analysis with meaning in life as predictor (T1), positive experiences with physical exercises and mobility as sequential mediators (T2), and physical QOL (T2) as the outcome was conducted.ResultsHigher meaning in life (T1) predicted more positive experiences with physical exercises (T2), which were associated with a higher level of mobility (T2), which in turn was associated with better physical quality of life (T2).ConclusionsMeaning in life at the beginning of inpatient rehabilitation may trigger positive experiences with physical exercises and functional changes in mobility levels, leading to better physical quality of life. Screening for low meaning in life may allow to identify patients who are at risk for a lack of improvement of mobility and physical quality of life during rehabilitation.