Aims Bicarbonate is involved in many human essential metabolic processes, but little is known about the association between serum bicarbonate and glucose metabolism. This study aims to investigate the association between serum bicarbonate and the risk of progressing to impaired fasting glucose (IFG)/diabetes mellitus (DM). Setting The data were obtained from a large-scale prospective cohort study in a single health centre in Beijing. Participants A total of 5318 participants aged 18-70 years who underwent health examinations annually with baseline fasting plasma glucose (FPG) ranging from 3.9 to 5.5 mmol/L, without a history of either diabetes or concomitant chronic diseases, were enrolled in this 6-year observational study. Primary outcome measures A logistic regression analysis was used to calculate ORs for progressing to IFG/DM by the category of baseline serum bicarbonate. In addition, an analysis of the receiver operating characteristic (ROC) curve for predicting IFG was performed. Results Of the 5318 participants, 210 developed IFG after a median 2.2 years of follow-up. After adjusting for sex, age, FPG, body mass index, systolic blood pressure, serum creatinine, serum alanine aminotransferase and low-density lipoprotein cholesterol at baseline, the participants in the first (OR 4.18, 95% CI 2.42 to 7.21; p < 0.001), second (OR 3.02, 95% CI 1.71 to 5.33; p < 0.001) and third (OR 2.12, 95% CI 1.15 to 3.89; p = 0.015) quartiles of serum bicarbonate had higher odds for progressing to IFG/DM compared with those in the highest quartile. The area under the ROC curve for predicting IFG/DM was 0.69 (95% CI 0.65 to 0.72; p < 0.001). Conclusions Lower serum bicarbonate is associated with higher risk of the development of IFG/DM.