Abstract Context Little is known about whether parity is associated with elevated early-pregnancy insulin resistance (IR), or whether overweight/obesity contributes to increasing the possible effect. Objective We determined the associations between parity and glucose metabolism parameters in the first trimester of pregnancy in a Mediterranean pregnant population, and whether these associations are affected by overweight/obesity. Methods A cross-sectional study was conducted of 264 healthy pregnant women from the ECLIPSES study who were recruited at 12 weeks of gestation. At baseline, details on socioeconomic status, obstetric history (including parity, ie, number of births), lifestyle factors, anthropometry, and blood samples were collected. Fasting serum glucose, insulin, and homeostasis model assessment of insulin resistance (HOMA-IR) index were assessed in the first trimester. Elevated IR was defined as the upper HOMA-IR tertile (≥1.58). Multivariable linear regression and Cox regression model with constant time were performed. Results Parity ranged from 0 to 4. After multivariable adjustment, the insulin levels (β [% change]: 20.92; 95% CI, 4.08-37.71) and HOMA-IR index (β [% change]: 19.72; 95% CI, 2.43-40.49) were positively associated with parity. Additionally, multiparous women, as compared to nulliparous, were more likely to have higher HOMA-IR levels (primiparous [1 birth], β [% change[: 16.88; 95% CI, −1.00 to 37.99; multiparous [≥2 births), β [% change]: 32.18; 95% CI, 3.56-68.71), and an increased relative risk (RR) of an elevated IR (primiparous [1 birth], RR: 1.55; 95% CI, 1.03-2.36; multiparous (≥2 births), RR: 1.72; 95% CI, 1.05-2.83). The combination of multiparity and overweight/obesity conferred a 3.04-fold increase in the RR of elevated IR, which increased proportionally to the number of parities. Conclusion This study demonstrates that parity may have a negative effect on early-pregnancy IR and that maternal overweight/obesity appears to further aggravate this relationship.