Background: More than 10 million Syrians have left their homes and sought refuge in neighboring countries, including Europe, since the beginning of the Syrian conflict in March 2011, and immigration continues to this day. This cross-sectional study included Syrian refugees residing in and around Hannover, Germany. We investigated whether general socioeconomic factors (e.g. age, sex, housing, asylum duration) were predictive factors for the quality of life (QOL) of Syrian refugees in Germany. Methods: The QOL of Syrian refugees was assessed using the WHOQOL-BREF tool, a questionnaire assessing the QOL in four domains: Physical health, psychological, social relationships and environment. A total of 114 Syrian refugees, aged between 18 and 45 years, who obtained one of the following statuses, asylum, refugee protection or subsidiary protection, were included. The QOL domain and total scores of Syrian refugees in Germany were compared with a Western norm and Sub-Saharan population. Data were analyzed with the Spearman Rho correlation coefficient, Kruskal–Wallis and Mann–Whitney U test and multivariate linear regression. Results: More than 65% of the participants (62.3% male, 37.7% female) were between 18 and 29 years old, and 45% had lived in Germany for less than four years. The lowest QOL score was reported in the social relationship’s domain (60.5%), while the psychological score was lowest in participants aged 40–45 years (P = 0.011). The age was significantly negatively associated with physical health (P = 0.010), psychological (P <  0.001) and the total QOL (P = 0.005). Asylum duration was associated with the environment domain (P = 0.040), the short-time refugees were less satisfied than the longtime refugees, and with aspects of the psychological domain in Enjoying life and Concentration ability (P <  0.001 and P = 0.033, respectively), yet was not associated with total QOL or total domain scores. There were significant associations between housing and the psychological domain (P = 0.032) and housing and the social relationship domain (P <  0.001). The refugees who living in camps registered a lower score in psychological than residents of apartments and houses, and the single refugees had a higher score than those married and divorced (P = 0.032 and P = 0.035, respectively). Conclusions: The Syrian refugees participating in this study showed a low QOL score in the assessment of all domains compared to the normal population, especially regarding social relations and psychological; it was associated with socioeconomic factors, such as housing, asylum duration and marital status. This calls for urgent societal and political efforts to strengthen the social living conditions of Syrian refugees in Germany.