BackgroundObstructive sleep apnea (OSA) during pregnancy is a risk factor for preeclampsia possibly through a link to placental physiology. This study evaluates the efficacy of continuous positive airway pressure (CPAP) on the modulation of blood pressure and the reduction in preeclampsia in women with high-risk pregnancy and OSA.MethodsA multicenter open-label, randomized controlled trial comparing CPAP treatment versus usual antenatal care was conducted in three academic hospitals in Bangkok, Thailand. Participants included singleton pregnant women aged older than 18 years with any high-risk condition (i.e., chronic hypertension, obesity, history of preeclampsia or gestational diabetes in the previous pregnancy, or diabetes), and OSA (respiratory disturbance index 5–29.99 events/hour by polysomnography), who presented either in the first trimester (gestational age, GA 0–16 weeks) or subsequently developed OSA during the 2nd trimester (GA 24–28 weeks). The primary endpoint was blood pressure during antenatal care. Secondary endpoints included the incidence of preeclampsia. An intention-to-treat analysis was performed with additional per-protocol and counterfactual analyses for handling of nonadherence.ResultsOf 340 participants, 96.5% were recruited during the first trimester. Thirty participants were later excluded leaving 153 and 157 participants in the CPAP and usual-care groups for the modified-intention-to-treat analysis. CPAP adherence rate was 32.7% with average use of 2.5 h/night. Overall, CPAP treatment significantly lowered diastolic blood pressure (DBP) by − 2.2 mmHg [95% CI (− 3.9, − 0.4),p= 0.014], representing approximately − 0.5 mmHg per hour of CPAP use [95%CI (− 0.89, − 0.10),p= 0.013]. CPAP treatment also altered the blood pressure trajectory by continuously lowering DBP throughout pregnancy with mean differences (95% CI) of − 3.09 (− 5.34, − 0.93), − 3.49 (− 5.67, − 1.31) and − 3.03 (− 5.20, − 0.85) mmHg at GA 18–20, 24–28, and 32–34 weeks, respectively compared to 0–16 weeks. Preeclampsia rate was 13.1% (20/153 participants) in the CPAP and 22.3% (35/157 participants) in the usual-care group with a risk difference (95% CI) of − 9% (− 18%, − 1%,p-value = 0.032) and a number-needed-to-treat (95% CI) of 11 (1, 21).ConclusionsCPAP treatment in women with even mild-to-moderate OSA and high-risk pregnancy demonstrated reductions in both DBP and the incidence of preeclampsia. CPAP treatment also demonstrated a sustained reduction in DBP throughout gestation.Trial registrationClinicalTrial.GovNCT03356106, retrospectively registered November 29, 2017.Supplementary InformationThe online version contains supplementary material available at 10.1186/s12931-023-02445-y.