The ‘Timed Up and Go’ test (TUG) is a widely used clinical tool for assessing gait and balance, relying primarily on timing as a measure. However, there are more observable biomechanical compensation strategies within TUG that are indicative of underlying neuromuscular issues and movement priorities. In individuals with unilateral knee osteoarthritis, an increased trunk flexion during TUG is a common phenomenon, often attributed to muscle weakness and/or pain avoidance. Unfortunately, differentiating between these underlying causes is difficult to accomplish using experimental studies. This study aimed to distinguish between muscle weakness and pain avoidance as contributing factors, using predictive neuromuscular simulations of the sit-to-walk movement.Muscle weakness was simulated by reducing the maximum isometric force of the vasti muscles (ranging from 20% to 60%), while pain avoidance was integrated as a movement objective, ensuring that peak knee load did not exceed predefined thresholds (2-4 times body weight). The simulations demonstrate that a decrease in muscular capacity led to greater trunk flexion. Pain avoidance led to slower movement speeds and altered muscle recruitments, but not to greater trunk flexion. The predictive simulations thus indicate that increased trunk flexion is more likely the result of lack of muscular reserve rather than pain avoidance. These findings align with reported differences in kinematics and muscle activations between moderate and severe knee osteoarthritis patients, emphasizing the impact of severe muscle weakness in those with advanced knee osteoarthritis. The simulations offer valuable insights into the mechanisms behind altered movement strategies, potentially guiding more targeted treatment.