The early prediction of atherosclerosis (AS) is important in the management of obstructive sleep apnea patients (OSA). MicroRNA (miRNA) plays a vital role in the evolution of OSA and AS. Its differential expression may therefore serve as a diagnostic and prognostic biomarker of AS in OSA. The aim of this study was to identify specific serummiRNAs that could serve as a novel screening signature of AS in OSA patients. The specificity and sensitivity of these miRNAs in the early diagnosis of AS in OSA patients were then determined. The 128 participants in this study underwent maximum carotid intima-media thickness (CIMT) measurements and polysomnography and were divided into 4 groups: 27 healthy volunteers with normal max-CIMT, 31 healthy volunteers with increased max-CIMT, 35 OSA patients with normal max-CIMT, and 35 OSA patients with iCIMT. MiRNA was extracted from the 12 participants' serum (3 participants each groups) and used to establish miRNA libraries for deep sequencing. A total of 116 participants were quantified by qRT-PCR. Correlations between differential expression of miRNAs and CIMT were assessed using the Spearman correlation coefficient. Our study was approved by the Ethics Committee of our hospital and was conducted in line with the Helsinki Declaration. MiR-664a-3p expression was quantified by qRT-PCR. Correlations between miR-664a-3p expression and CIMT were assessed using the Spearman correlation coefficient. The results showed that the miR-664a-3p was downregulated in the OSA, OSA with iCMIT, and nCIMT groups compared with the control group. The demonstrated potential of circulating miR-664a-3p as a noninvasive marker of AS in essential OSA patients should be confirmed in further studies.