Obstructive sleep apnea (OSA) can cause sleep fragmentation and intermittent hypoxemia, which are linked to oxidative stress. White matter changes (WMCs) representing cerebrovascular burden and are at risk factor for oxidative ischemic injury. The current study explores the mutual relationships between OSA and WMCs. We performed a systematic review of electronic databases for clinical studies investigating OSA and WMCs. Random-effects models were used for pooled estimates calculation. A total of 22 studies were included in the meta-analysis. The results revealed a significantly higher prevalence rate of WMCs odds ratio (OR) 2.06, 95% confidence interval (CI) 1.52–2.80, p  < 0.001 and significantly higher severity of WMCs (Hedges’ g  = 0.23, 95% CI 0.06–0.40, p  = 0.009) in the patients with OSA than in controls. Furthermore, the results revealed a significantly higher apnea–hypopnea index (Hedges’ g  = 0.54, 95% CI 0.31–0.78, p  < 0.001) and significantly higher prevalence rate of moderate-to-severe OSA (OR 2.86, 95% CI 1.44–5.66, p  = 0.003) in the patients with WMCs than in controls, however there was no significant difference in the prevalence rate of mild OSA between the patients with WMCs and controls (OR 0.71, 95% CI 0.20–2.54, p  = 0.603). OSA was associated with a higher prevalence and more severe WMCs, and the patients with WMCs had an increased association with moderate-to-severe OSA. Future large-scale randomized controlled trials with a longitudinal design are essential to further evaluate treatment in patients with OSA.