Although polysomnography is the gold standard method to diagnose obstructive sleep apnea syndrome (OSAS), there is an ongoing quest for simpler and relatively inexpensive biomarkers of disease presence and severity. To address this issue, we conducted a systematic review of the potential diagnostic role of the red blood cell distribution width (RDW), a routine hematological parameter of red blood cell volume variability, in OSAS. A total of 1478 articles were initially identified in the databases PubMed, Web of Science, Scopus, Embase, and Google Scholar, from their inception to February 2023, and 20 were selected for final analysis. The RDW was significantly higher in OSAS than in non-OSAS subjects (SMD = 0.44, 95% CI 0.20 to 0.67,p< 0.001; low certainty of evidence). In univariate meta-regression, the mean oxygen saturation (SpO2) was significantly associated with the effect size. No significant between-group differences were observed in subgroup analyses. Notably, in OSAS subjects, the RDW SMD progressively increased with disease severity. In conclusion, these results suggest that the RDW is a promising biomarker of OSAS (PROSPERO registration number: CRD42023398047).