The majority of studies on psoriasis have focused on explaining the genetic background and its associations with the immune system’s response. The aim of this study was to identify the low-molecular weight compounds contributing to the metabolomic profile of psoriasis and to provide computational models that help with the classification and monitoring of the severity of the disease. We compared the results from targeted and untargeted analyses of patients’ serums with plaque psoriasis to controls. The main differences were found in the concentrations of acylcarnitines, phosphatidylcholines, amino acids, urea, phytol, and 1,11-undecanedicarboxylic acid. The data from the targeted analysis were used to build classification models for psoriasis. The results from this study provide an overview of the metabolomic serum profile of psoriasis along with promising statistical models for the monitoring of the disease.