IntroductionSome studies indicate that persistent somatic symptoms (PSS) are more prevalent among individuals with a low socioeconomic status (SES) and a migration background. However, factors explaining social inequalities in PSS are largely unknown. It is expected that aggravating factors of PSS like illness perception, illness beliefs (health literacy, stigma), illness behaviour and health anxiety may play an important role for this explanation. The SOMA.SOC study will examine social inequalities (according to SES and migration) in factors contributing to symptom persistence in irritable bowel syndrome (IBS) and fatigue.Methods and analysisThe project will collect both quantitative and qualitative data. Quantitative data will be gathered via a representative telephone survey in Germany (N=2400). A vignette design will be used depicting patients varying in sex, condition (IBS/fatigue), occupational status (low/high) and migration (yes/no). In the survey, we will assess public knowledge and beliefs (eg, health literacy), attitudes (stigma) and personal experiences with the condition (eg, somatic symptom burden). Complementary, longitudinal qualitative interviews will be conducted with patients (n=32 at three time points, resulting in N=96 interviews) who will also vary according to sex, condition, occupational status and migration. Patients will be recruited from primary care practices in Hamburg. The interviews will cover origin and development of the condition, coping and help-seeking as well as social interactions and perception of the disease by others (eg, perceived stigma). SOMA.SOC is part of the interdisciplinary SOMACROSS (Persistent SOMAtic Symptoms ACROSS Diseases) research unit.Ethics and disseminationThe study protocol was approved by the Ethics Committee of the Hamburg Medical Association on 25 January 2021 (reference number: 2020–10194- BO-ff). Informed consent will be obtained from all participants. The main findings will be submitted for publication in peer-reviewed journals within 12 months of study completion.