Objective To analyze serum levels of inhibitory costimulatory molecules and their correlations with innate immune cytokine levels in patients with pulmonary tuberculosis (PTB). Methods Data for 280 PTB patients and 280 healthy individuals were collected. Serum levels of immune molecules were measured using ELISA. Univariate, multivariate, subgroup, matrix correlation, and receiver operating characteristic curve analyses were performed. Results Host, environment, lifestyle, clinical features, and medical history all influenced PTB. Serum levels of soluble programmed death ligand 1 (sPD-L1), soluble T-cell immunoglobulin- and mucin-domain–containing molecule 3 (sTim-3), soluble galectin-9 (sGal-9), interleukin (IL)-4, and IL-33 were significantly higher in patients with PTB, while levels of IL-12, IL-23, IL-18, and interferon (IFN)-γ were significantly lower. Serum levels of sTim-3 were higher in alcohol users. Levels of sTim-3 were negatively correlated with those of IL-12. Levels of IL-12, IL-23, and IL-18 were positively correlated with those of IFN-γ, while levels of IL-12 were negatively correlated with those of IL-4. The areas under the curve of sPD-L1, sTim-3, sGal-9, IL-12, IL-23, IL-18, IFN-γ, IL-4, and IL-33 for identifying PTB were all >0.77. Conclusions Inhibitory costimulatory molecules may be targets for controlling PTB. Immune molecules may be helpful for diagnosis of PTB.