Purpose The main purpose of this study was to assess health-related quality of life (HRQoL) among Syrian refugees resettled in Sweden. Further, we wanted to investigate whether sex, age, education, area of residence, cohabitation and social support were associated with HRQoL in this population. Methods This is a cross-sectional study including 1215 Syrian refugees from a randomly selected sample frame resettled in Sweden between the years 2011 and 2013. HRQoL was measured by the EQ-5D-5L descriptive system, and EQ-5D-5L index values were calculated. Associations between sex, age, education, area of residence, cohabitation, social support and EQ-5D-5L were investigated using multiple linear regression analysis. Results Depression/anxiety was the most commonly (61.9%) reported EQ-5D-5L problem among the group of Syrian refugees. The mean EQ-5D-5L index value was found to be 0.754. Male sex, younger age, cohabitation and social support were found associated with a higher EQ-5D-5L index score. Conclusions Our results concerning long-lasting health problems among the study population indicate that there is a profound need for policies and interventions promoting refugees' health. Our results also show that social support, a modifiable factor, is relevant to refugees' overall health, pointing to the importance of public health interventions and policies targeting the facilitation, mobilization and enhancing of refugees' social support.