Evidence supports that physical activity (PA) improves symptoms of multiple sclerosis (MS). Although application of principles from Social Cognitive Theory (SCT) may facilitate positive changes in PA behaviour among people with multiple sclerosis (pwMS), the constructs often explain limited variance in PA. This study investigated the extent to which MS symptoms, including fatigue, depression, and walking limitations combined with the SCT constructs, explained more variance in PA than SCT constructs alone among pwMS.Baseline data, including objectively assessed PA, exercise self-efficacy, goal setting, outcome expectations, 6-min walk test, fatigue and depression, from 65 participants of the Step It Up randomized controlled trial completed in Ireland (2016), were included. Multiple regression models quantified variance explained in PA and independent associations of (1) SCT constructs, (2) symptoms and (3) SCT constructs and symptoms.Model 1 included exercise self-efficacy, exercise goal setting and multidimensional outcomes expectations for exercise and explained similar to 14% of the variance in PA (R (2)=0.144, p < 0.05). Model 2 included walking limitations, fatigue and depression and explained 20% of the variance in PA (R (2)=0.196, p < 0.01). Model 3 combined models 1 and 2 and explained variance increased to similar to 29% (R (2)=0.288; p < 0.01). In Model 3, exercise self-efficacy (beta=0.30, p < 0.05), walking limitations (beta=0.32, p < 0.01), fatigue (beta = -0.41, p < 0.01) and depression (beta = 0.34, p < 0.05) were significantly and independently associated with PA.Findings suggest that relevant MS symptoms improved by PA, including fatigue, depression and walking limitations, and SCT constructs together explained more variance in PA than SCT constructs alone, providing support for targeting both SCT constructs and these symptoms in the multifactorial promotion of PA among pwMS.