BACKGROUND Hypercapnia is abnormally high arterial partial pressure of carbon dioxide (CO₂). CO₂ can affect redox signaling mechanisms, leading to production of oxidative derivatives. Thiol is formed by attaching a sulfhydryl group to a carbon atom. Under oxidative stress, it forms covalent bonds called thiol disulphide bonds. Serum albumin is modified to ischemia-modified albumin (IMA) by exposure to free radicals. This case-control study aimed to evaluate thiol/disulphide homeostasis and IMA levels in 61 patients with hypercapnia. MATERIAL AND METHODS We studied 61 patients with hypercapnia and 61 normocapnic volunteers in the control group, between May 2018 and January 2019; 56 of these patients were diagnosed with chronic obstructive pulmonary disease and 5 of them were diagnosed with obstructive sleep apnea syndrome. Arterial blood samples analyzed by using the Ellman reagent for thiol/disulphide data. A colorometric assay was used for detection of IMA levels. RESULTS Native thiol and total thiol values in the hypercapnic group were significantly lower than in the control group (P=0.024, P=0.006 respectively), as IMA values were significantly higher (P<0.001). There was no statistically significant difference between the hypercapnic and control groups in terms of disulphide, disulphide/native thiol, disulphide/total thiol, and native thiol/total thiol values (P>0.05). CONCLUSIONS In hypercapnic patients, there are changes in thiol/disulphide homeostasis and IMA levels. All significant differences in this study support that changes in thiol disulphide homeostasis and IMA in hypercapnic patients are indicators of oxidative stress.