The purposes of this prospective, longitudinal study were to examine the relationships between leptin, human chorionic gonadotropin (hCG), cortisol, and psychosocial stress and nausea and vomiting (NV) in women with mild-to-moderate NV throughout pregnancy. Participants comprised 91 pregnant women recruited from prenatal clinics in southern Taiwan. Data analysis using one-way analysis of variance (ANOVA) indicated that leptin, hCG, cortisol levels, and Index of Nausea, Vomiting, and Retching (INVR) scores, but not stress (measured with the Visual Analog Scale, VAS) scores, were significantly different among the three trimesters. The average INVR score and hCG level decreased from the first to third trimesters (p < .0001 for both). The average leptin and cortisol levels increased from the first to third trimesters (p = .001 and p < .0001, respectively). Analysis using mixed models indicated that the INVR scores decreased significantly in a progressive manner through the stages of pregnancy and were significantly lower in the second and third trimesters. Findings reveal that stress/VAS and hCG may both be significantly and independently associated with INVR scores. Future research should examine psychosocial reactions in addition to exploring other biochemical markers related to NV and stress.