A new study published in the journal ofCureusshowed that Maternal age, BMI, weight gain, and history of gestational diabetes mellitus (GDM) remain strong predictors of GDM. Further first-trimester neutrophil counts showed no predictive value, limiting their use as early inflammatory markers. GDM, is associated with severe hazards for both the mother and the newborn, including polyhydramniosis and the fetal risk of large for gestational age (LGA). In this study, women who frequent National Guard primary care clinics in Jeddah, Saudi Arabia, were asked to rate the predictive value of first-trimester complete blood count (CBC) characteristics, namely the neutrophil count, for the onset of GDM. Included were pregnant women between the ages of 18 and 45 who received GDM screening at weeks 24 and 28 and finished first-trimester laboratory testing. Women with chronic conditions, diabetes, or indications of persistent infections were not included. IBM SPSS Statistics for Windows, Version 29 (published in 2022; IBM Corp., Armonk, NY, USA), was used to analyze clinical, laboratory, and pregnancy outcome data. GDM developed in 25.6% of the 399 women. A history of prior GDM, a higher body mass index (BMI), excessive prenatal weight gain, and greater maternal age were all significant predictors (p < 0.001). RBC and fasting glucose counts were higher in the GDM group, according to laboratory results, but the neutrophil count and neutrophil-to-lymphocyte ratio (NLR) were not statistically significant predictors. The 1-hour oral glucose tolerance test (OGTT) result, total weight increase, and prior history of GDM were all found to be independent predictors by logistic regression, with OGTT exhibiting the highest correlation (OR = 3.878, p < 0.001). Overall, the development of GDM is still significantly predicted by established risk variables, including maternal age, BMI, total gestational weight gain, and a previous history of GDM. These results do not support the routine use of inflammatory markers in first-trimester screening, even though they have been suggested as early predictors. These indicators include neutrophil count and NLR. The best independent predictor was the one-hour OGTT value. Alzahrani, A. M., Alharbi, N. S., Alageel, N., Alharbi, M. H., & Qattan, D. A. (2025). First-trimester complete blood count as a predictor of gestational diabetes mellitus: A multi-center primary health care study. Cureus, 17(7), e89147.https://doi.org/10.7759/cureus.89147