The objective of this study was to identify the association between emotional distress and social support networks with quality of life in primary care patients. This was a cross-sectional study involving 1,466 patients in the cities of São Paulo and Rio de Janeiro, Brazil, in 2009/2010. The General Health Questionnaire, the Hospital Anxiety and Depression Scale and the brief version of the World Health Organization Quality of Life Instrument were used. The Social Support Network Index classified patients with the highest and lowest index as socially integrated or isolated. A bivariate analysis and four multiple linear regressions were conducted for each quality of life outcome. The means scores for the physical, psychological, social relations, and environment domains were, respectively, 64.7; 64.2; 68.5 and 49.1. In the multivariate analysis, the psychological domain was negatively associated with isolation, whereas the social relations and environment domains were positively associated with integration. Integration and isolation proved to be important factors for those in emotional distress as they minimize or maximize negative effects on quality of life.