OBJECTIVE: To investigate the association of serum progesterone in first trimester with low birth weight (LBW, birth weight <2500 g) and other adverse pregnancy outcomes including hypertensive disorders of pregnancy, preterm delivery, premature rupture of membranes at term, and preterm premature rupture of membranes in a general population. METHODS: We conducted a cohort study of 263 women with low-risk singleton intrauterine pregnancies who had a spot serum progesterone measurement in the first trimester in a Singapore tertiary maternity hospital. Study outcomes were retrieved from clinical records. Follow-up data were available for 131 women. Univariate and multivariate logistic regression analyses were performed to assess the association of low serum progesterone (<35 nmol/L) with LBW and other adverse pregnancy outcomes. RESULTS: Low serum progesterone was associated with a significantly increased risk of LBW (adjusted odds ratio: 5.28 [1.02, 27.3]; p=0.047). Low serum progesterone was associated with a significantly increased risk of hypertensive disorders of pregnancy in univariate analysis (unadjusted odds ratio: 8.43 [1.31, 54.2]; p=0.025). CONCLUSION: Low serum progesterone in the first trimester is a significant risk factor for LBW and possibly other placental dysfunction disorders such as hypertensive disorders of pregnancy. Further studies with larger sample sizes are needed to confirm the associations.