The link between post-migration stressors and mental ill health is well documented in refugees resettled in high-income host countries, but the consequences of these stressors on refugees’ health-related quality of life (HRQoL) are less known. This study examined the association between post-migration stressors and HRQoL among Syrian adult refugees resettled in Sweden using a preference-based value set obtained from the general Swedish population. A total of 1215 Syrian adults, ages 18–64 years, granted residency in Sweden, responded to a postal questionnaire in 2016 regarding various aspects of their resettlement. The European Quality of Life Five Dimensions Five Level (EQ–5D–5L) questionnaire was used to assess HRQoL through an EQ–5D–5L index score (range; 0=dead to 1=full health). The index score was preference weighted using a Swedish population value set. Predictors were four self-reported post-migration stressors related to daily living in the host country: financial strain, social strain, competency strain and perceived discrimination divided into low, medium and high levels of experienced stress. Multivariable linear regression models were employed to assess the association between post-migration stressors and HRQoL index score, adjusting for potentially traumatic events in the pre- and peri-migration phase as well as sociodemographic confounders/covariates (sex, age, education, civil status, immigration year). The Syrian refugees had a mean EQ–5D–5L index score of 0.863 (SD = 0.145). There was strong evidence of a negative dose-response association in both unadjusted and adjusted models between HRQoL and the post-migration stressors financial strain and social strain—i.e., there was a stepwise, and statistically significant, decrease in HRQoL when going from low to medium to high strain. Competency strain and discrimination were only associated with lower HRQoL when experienced at high levels in fully adjusted models. High exposure to potentially traumatic experiences before or during flight was also associated with lower HRQoL. Syrian refugees resettled in Sweden reported a lower HRQoL than the general Swedish population and lower than age-matched Swedish adults. The present study results point to the possible adverse effects of post-migration stressors on HRQoL.