Abstract Purpose Sleep apnea syndrome (SAS) is a relatively common disorder, but many patients with SAS are still undiagnosed. Using Japanese annual health check and medical claims data, we analyzed the association between hemoglobin upswing, defined as an increase in hemoglobin level within the reference range, and the incidence of SAS. Methods In this study, we used the Japan Medical Database Center (JMDC) annual health check and medical claims data of 351,930 male individuals aged 40−59 who had their hemoglobin concentration checked in 2014. We initially identified the reference range of hemoglobin level based on the mean and the standard deviation of hemoglobin concentration in this population. We examined the effect of hemoglobin upswing on the incidence of SAS using Cox proportional hazards models. Results The hemoglobin upswing was defined as a change greater than 1.19 g/dL in the reference range of 13.1 to 17.2 g/dL. During a mean follow-up period of approximately 1285 days, 1.9% of the individuals with hemoglobin upswing were diagnosed with SAS, while 1.6% of those without hemoglobin upswing were diagnosed with SAS. The hazard ratio of hemoglobin upswing to the incidence of SAS was 1.21 (95% CI; 1.01–1.44, p = 0.04). Conclusion We herein revealed the association between hemoglobin upswing and the incidence of SAS in a middle-aged male population. A statistically significant increase in hemoglobin concentration even in the reference range should be paid attention to as it may indicate the presence of SAS.