Cardiovascular (CV) disease, such as heart disease, stroke and CV death, are well-established complications of Obstructive Sleep Apnea (OSA). However, it has not been demonstrated the effect of continuous positive airway pressure (CPAP) on the prevention of CV events. It is imperative to identify useful biomarkers to determine patients that could benefit from such treatment. The value of ischemia-modified albumin (IMA) was analyzed and its relationship with CV risk in OSA patients. 1181 (82% males, median age: 58 years, Body Mass Index: 29.2 kg/m2) patients from the ISAACC (NCT01335087; n: 1008) and bioSAOS (n: 173) cohorts were included. All patients underwent a sleep study for OSA diagnosis and blood samples analysis for IMA determination. IMA values were significantly higher in moderate and severe OSA [mean (IQR) 33.7 (19.8-59.9) (U/l); 35 (19.3-59.8) (U/l), p: 0.004 respectively] than in patients without or with mild OSA [28.3 (13.2-52.4)(U/l)]. The IMA levels were positively correlated with the AHI and were related to high blood pressure and a procoagulation status in these patients. In conclusion, for patients with high CV morbidity, IMA was related to OSA severity. This biomarker could be useful to determine the CV risk added by OSA in these types of patients.