Alcohol, a muscle relaxant, can potentially worsen obstructive sleep apnea (OSA) but the literature on the effects of alcohol on OSA is conflicting. This systematic review and meta-analysis of randomized controlled trials examined the impact of alcohol on breathing parameters during sleep. Ovid Medline, Embase and PsycINFO databases were queried through November 1, 2017 for studies that reported objective measures of breathing during sleep, prior to and after alcohol administration. Weighted mean differences (WMD) and 95% confidence intervals (CI) were calculated for apnea-hypopnea index (AHI) and mean oxyhemoglobin saturation (SpO2). Secondary outcome measures were examined where available. The meta-analysis of 14 eligible studies (n = 422; 71.9% male) found that AHI increased significantly after alcohol administration (WMD = 2.33; 95% CI = 1.41 to 3.25, I² = 62%) and mean SpO2 was significantly reduced (WMD = −0.60; 95% CI = −0.72 to −0.49, I² = 0%). The increase in AHI was greater in snorers (WMD = 4.20; 95% CI = 1.19 to 6.50, I² = 0%) and those with a diagnosis of OSA (WMD = 7.10; 95% CI = 3.59 to 10.61, I² = 0%). Additionally, a significant increase in respiratory event duration (WMD = 0.86; 95% CI = 0.18 to 1.55, I² = 19%) and decrease in nadir SpO2 (WMD = −1.25; 95% CI = −2.00 to −0.50, I² = 25%) were noted. Alcohol is a modifiable risk factor that can result in the development or worsening of OSA.