The ageing population has led to recent increases in musculoskeletal conditions, with muscle weakness a major contributor to functional decline. Understanding the early phases of muscle weakness will help devise treatments to extend musculoskeletal health. Little is understood of the effects of muscle weakness on everyday activities such as sit-to-stand, a determinant of mobility that, in the early stages of weakness, requires upper limb compensation. This experimental and computational modelling study investigated the effects of muscle weakness on upper-extremity muscle forces of 27 healthy adults when using arm rests. Weakness of 29 upper limb muscles was simulated by individually removing each from a musculoskeletal model. Serratus anterior weakness was highlighted as detrimental, with the model unable to fully solve the loadsharing redundancy in its absence, and forces at the elbow and glenohumeral joint and in other muscles were found to be profoundly increased. Its large number of fast-twitch muscle fibres, predisposed to atrophy with age, highlight the centrality of the serratus anterior as a key determinant of mobility in this critical task and a potential source of early immobility through its preferential loss of strength and thus point to the requirement for early clinical interventions to mitigate loss.