Aim: To study the relationship between NLRP3 (nucleotide oligomerization domain [NOD]-, leucine-rich repeats [LRR]-, and pyrin domain-containing protein 3) inflammasome and its downstream inflammatory factors in obstructive sleep apnea (OSA) patients with carotid atherosclerosis (CAS) under cigarette exposure, further exploring the risk factors of CAS in OSA patients. Methods: A total of 109 adult males who underwent polysomnography and carotid artery ultrasonography in our hospital from October 2019 to December 2021 were selected. According to the detection results, they were divided into the OSA group, the CAS group, and the OSA combined CAS group; additionally, 29 healthy subjects who underwent a physical examination were also included. According to whether they were smoking, the groups were further divided into smoking and non-smoking groups. The age, body mass index (BMI), blood pressure, apnea-hypopnea index (AHI), lowest blood oxygen saturation (LSaO2), carotid intima-media thickness (CIMT), levels of blood sugar, blood low-density lipoprotein cholesterol (LDLc), and serum NLRP3, interleukin-1β (IL-1β), and interleukin-18 (IL-18) of all subjects were recorded. Results: The OSA combined CAS group had higher LDLc levels and AHI and lower LSaO2 than the OSA group and CAS group. The levels of serum NLRP3, IL-1β, and IL-18 in the OSA group were higher than those in the normal control group (P < 0.05); and those in the OSA combined CAS group were higher than the OSA group and CAS group (P < 0.05), regardless of cigarette exposure. Considering cigarette exposure, serum NLRP3, IL-1β, and IL-18 levels were higher in the OSA, CAS, and OSA combined CAS smoking groups than those in the non-smoking group (P < 0.05). Under cigarette exposure, AHI, LDLc, NLRP3, IL-1β, and IL-18 were significantly positively correlated (P < 0.05), and LSaO2 was negatively correlated with CAS in OSA (P < 0.05). AHI, LSaO2, LDLc, NLRP3, and IL-1β are the risk factors for OSA combined with CAS. Conclusion: LSaO2, AHI, LDLc, NLRP3, and IL-1β are the important risk factors for OSA combined with CAS under cigarette exposure, and their levels can be used to predict the occurrence of CAS in OSA.