Objective: The objective was to describe the individual items of the environmental factors and to investigate the relationship between the environmental factors to health conditions, general health and quality of life in people with SCI in South Africa. Methods: Two hundred persons with SCI participated in a cross-sectional survey design. This study formed part of the International Spinal Cord Injury (InSCI) Community Survey. Four major domains, environmental factors, health conditions, general health and quality of life of the survey questionnaire responses, were used for the analysis. Regression models were used to determine the association between the independent variable, which consisted of the specific environmental factors items, and the dependent variables comprising health conditions, general health and quality of life. Results: The commonly reported environmental barriers were public access, lack of short- and long-distance transport and finances. Environmental factors such as public access (p< 0.001), short- (p< 0.001) and long-distance transport (p= 0.001), and friends’ (p= 0.003) and colleagues’ (p< 0.001) attitudes and communication (p= 0.042) were significantly associated with the presence of secondary health conditions. Finances (p= 0.026), family attitudes (p= 0.037) and communication (p= 0.039) had a significant association with worsened mental health. Services (p= 0.022) and communication (p= 0.042) were also significantly associated with decreased general health. Conclusion: The results provide insight into modifiable environmental factors policymakers need to consider or adapt to improve the lives of people with SCI in South Africa with respect to health (secondary health conditions), as well as general and mental health.