The specific role of weight change in the first weeks of gestation in fetal growth has not been fully explored in humans. Our aims were to investigate: (1) the specific association between weight change in the first trimester of pregnancy (WCT1) and size at birth in term pregnancies; and (2) the role of placental weight in this relationship. From 2002 women included in the French EDEN study, 1744 mother–child pairs reached term, had pre-pregnancy weight available and at least five measures of weight in pregnancy. We extrapolated women's weight at each week of gestation with a three-degree polynomial model and estimated weight change during each trimester of gestation. We used a multivariate linear model to investigate the associations between WCT1 and birth size after taking into account potential confounders (age, parity, BMI, tobacco use, educational level, length of gestation, newborn gender, weight change after the first trimester and centre of study). Then, we performed path analysis to investigate whether the relation between WCT1 and birth size could be mediated by placental weight. After taking into account weight gain in later gestation, WCT1 was positively associated with birthweight. Results of path analysis showed that there was no direct association between WCT1 and birth size, but that this association was mediated by placental weight. Weight change during the first weeks of pregnancy may impact on fetal growth independently of weight change later in pregnancy through its effects on placental growth and function.