The 2'-5' oligoadenylate synthetase (OAS)family, comprising OAS1, OAS2, OAS3, and OASL, has been shown to participate in the host immune response against Mycobacterium tuberculosis (Mtb). However, their expression profiles in tuberculosis (TB) remain inconsistent. In two TB-related datasets, the OAS family exhibits contrasting expression trends. To further investigate, we examined the expression of the OAS family in whole blood, peripheral blood mononuclear cells (PBMC), and pleural fluid mononuclear cells (PFMC) as study samples, focusing on pulmonary tuberculosis (PTB) and tuberculous pleuritis (TPE). The results revealed differing expression patterns of the OAS family in the two diseases. In PFMC samples from TPE patients, the OAS family showed overall upregulation. Additionally, matched samples from nine TPE patients indicated overlapping expression of the OAS family in both PBMC and PFMC samples.