ABSTRACT: The objective of this study was to evaluate the independent associations between nausea, vomiting, fatigue and health-related quality of life of women in early pregnancy in the Generation R study, which is a prospective mother and child cohort. Analyses were based on 5079 women in early pregnancy in the Rotterdam area, the Netherlands. The information on nausea, vomiting and fatigue in the previous three months was measured in the questionnaire at enrollment, as well as potential confounders (i.e., maternal/gestational age, ethnic background, educational level, parity, marital status, body mass index, tobacco and alcohol use, chronic/infectious conditions, uro-genital conditions/symptoms, sleep quality, headache, anxiety, and depression). Health-related quality of life was assessed by the 12-item Short Form Health Survey and physical and mental component summary scores were calculated. Multivariate regression models were performed to evaluate the independent associations of the presence of nausea, vomiting and fatigue with health-related quality of life, adjusting for potential confounders. 33.6% of women experienced daily presence of nausea, 9.6% for vomiting and 44.4% for fatigue. Comparing with women who never reported nausea, vomiting and fatigue, women with daily presence of at least one of these symptoms had significantly lower scores of physical component summary and mental component summary, after adjusting for potential confounders. Our study shows how common nausea, vomiting and fatigue are among women in early pregnancy and how much each of these symptoms negatively impact on health-related quality of life. We call for awareness of this issue from health care professionals, pregnant women and their families.