In this paper, we have compared the classifier algorithms including C4.5 decision tree, le artificial neural network (ANN), artificial immune recognition system (AIRS), and adaptive neuro-fuzzy inference system (ANFIS) in the diagnosis of obstructive sleep apnea syndrome (OSAS), which is an important disease that affects both the right and the left cardiac ventricle. The goal of this study was to find the best classifier model on the diagnosis of OSAS. The clinical features were obtained from Polysomnography device as a diagnostic tool for obstructive sleep apnea in patients clinically suspected of suffering this disease in this study. The clinical features are arousals index, apnea–hypopnea index (AHI), SaO2 minimum value in stage of rapid eye movement, and percent sleep time in stage of SaO2 intervals bigger than 89%. In our experiments, a total of 83 patients (58 with a positive OSAS (AHI′>′5) and 25 with a negative OSAS such that normal subjects) were examined. The decision support systems can help to physicians in the diagnosing of any disorder or disease using clues obtained from signal or images taken from subject having any disorder. In order to compare the used classifier algorithms, the mean square error, classification accuracy, area under the receiver operating characteristics curve (AUC), and sensitivity and specificity analysis have been used. The obtained AUC values of C4.5 decision tree, ANN, AIRS, and ANFIS classifiers are 0.971, 0.96, 0.96, and 0.922, respectively. These results have shown that the best classifier system is C4.5 decision tree classifier on the diagnosis of obstructive sleep apnea syndrome.