Season of birth (SOB) has been investigated as one of the environmental factors that might epigenetically determine the physiology of individuals. This study investigated the role of SOB in the association between Quality of Life (QOL), a proxy of psychological stress status, and C-reactive protein (CRP) concentration (i.e., inflammatory status) among 1,085 adults (aged 20-57 years old) in Hainan Island, China. High sensitivity CRP concentration was measured in dried blood spot samples, while the abbreviated version of the World Health Organization's QOL questionnaire was used to gather information on six QOL domains. Analysis stratified by three historically distinct age groups revealed a significant association between CRP concentration, SOB, QOL and an interaction between SOB and QOL among the youngest and oldest groups. In the oldest group, those born in the dry season had a higher CRP concentration with worse QOL whereas in the youngest group, there was a higher CRP concentration with better QOL. Annual per capita rice production, a proxy of population nutritional status in the year of birth, was found to predict CRP concentration only among the second oldest group. These findings suggest that the early environment might affect the immune response to psychological stress in adulthood and that its effect may differ by the time period in which people were born.