Several studies highlighted a correlation between exhaled air volatile organic compounds (VOCs) and some pathological conditions, such as chronic kidney disease (CKD), chronic liver disease, etc. In fact, in literature has been reported that CKD is characterized by an increased concentration of ammonia, trimethylamine (TMA) and isoprene compared to healthy subjects. Currently, there is not a validate and standardized method to detect VOCs. For this purpose, we examined the utility of selected ion flow tube-mass spectrometry (SIFT-MS) to measure VOCs in CKD patients and we evaluated the possible correlation between VOCs and the presence of CKD and its stage. We enrolled 68 CKD patients under conservative therapy and 54 healthy subjects. The analysis of the VOCs of the exhaled air of the enrolled subjects was performed by SIFT-MS. Among all the VOCs analyzed, the most relevant results by ROC curves were observed for TMA, acetone, ammonia and dimethyl sulfide. We found that a breath TMA concentration superior to 26 ppbv characterizes a 6.11 times greater risk of CKD, compared to subjects with lower levels. Moreover, we detected an increased concentration of acetone and ammonia in CKD patients compared to healthy subjects. We highlight the potential utility of SIFT-MS in CKD clinical management.Clinical trial registry: R.S. 15.19 of 6 February 2019.