Objective: Limited evidence examines the association of psychological factors, such as fear of movement and pain catastrophizing, with musculoskeletal pain patterns in active manual wheelchair users with spinal cord injury (SCI). This study investigated the relationship among musculoskeletal pain, fear avoidance factors, quality of life (QoL), activity and duration of injury in individuals with SCI. Design: Cross-sectional correlational. Setting: Community setting. Participants: Twenty-six individuals with SCI (age = 42 ± 14 years, duration manual wheelchair use = 17 ± 13 years, work/school/volunteer hours/week = 31 ± 14; recreation/sports hours/week 10 ± 12). Outcome Measures: Demographics and self-report measures including the Musculoskeletal Pain Survey (MPS), Wheelchair Users Shoulder Pain Index (WUSPI), Tampa Scale of Kinesiophobia (TSK-11), Pain Catastrophizing Scale (PCS), Fear of Pain (FPQ), Subjective Quality of Life Questionnaire (SQoL), and the Social Interaction Inventory (SII). Spearman’s rho (ρ) assessed correlation among measures. Results: Strong association existed between age and duration of injury (ρ = 0.66, P < 0.001). SQoL offered a strong, direct correlation with age (ρ = 0.63, P = 0.01), duration of injury (ρ = 0.70, P = 0.001), and strong, inverse relationship with MPStotal (ρ = −0.66, P = 0.003) and MPS shoulder subscore (ρ = −0.64, P = 0.004). WUSPI demonstrated strong, inverse association with self-reported work hours (ρ = −0.52, P = 0.02) and a strong, direct relationship to PCS (ρ = 0.79, P = <0001). PCS demonstrated a strong, inverse relationship to work/school/volunteer hours (ρ = 0.71, P < 0.001) and strong association to TSK-11_total (ρ = 0.61, P = 0.001). A moderate, inverse relationship was identified for recreational/sports hours and FPQ (ρ = 0.48, P = 0.03). Conclusion: This cyclical relationship of musculoskeletal pain, reduced activity, and maladaptive psychological factors allude to interdependence of factors, supporting the multidisciplinary approach to care.