Background Physical symptoms such as fatigue, pain, digestive problems, and sleep disturbances are chief reasons individuals seek primary care, as they affect health-related quality of life. We investigated the associations between various combinations of these common symptoms and individuals’ health-related quality of life. Methods This large-scale survey study of 1100 Koreans aged ≥19 years was conducted in 2017 using multi-stage stratified sampling based on region, sex, and age. Data were collected using questionnaires administered face-to-face; then, a linear regression analysis was performed to assess how the symptoms were related to participants’ health-related quality of life. Complex symptoms were defined as co-occurrence of two or more of the four symptoms—fatigue, pain, digestive problems, and sleep disturbances. Results The most frequently observed stand-alone symptom was fatigue, while the most common combination was fatigue and pain. When examined individually, fatigue, digestive problems, and sleep disturbances were closely associated with mental health-related quality of life, and pain was associated with physical health-related quality of life. Complex symptoms were also related to health-related quality of life. Lower physical health-related quality of life was strongly associated when fatigue and pain or all four symptoms were co-occurring, and the lowest mental health-related quality of life was seen when all four symptoms were present, after adjusting for all variables. Conclusions Symptoms can be present in various combinations and are significantly associated with health-related quality of life. Extra attention should be given to patterns accompanying fatigue and pain and to those involving more symptoms. This elucidated the characteristics of symptoms that affect the health-related quality of life of South Korean adults.

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