OBJECTIVE: Pregnancy with pulmonary hypertension (PPH) is one of the main causes of maternal heart failure and death. Endocan is a well-established soluble proteoglycan biomarker for endothelial dysfunction and inflammation. The Indoleamine 2, 3 dioxygenase (IDO) enzyme family comprises IDO1, IDO2, and TDO2, with IDO1-dependent tryptophan metabolites being particularly promising as candidate biomarkers for pulmonary hypertension (PH). However, there have been no reports on the relationship between endocan and IDO1-dependent metabolite and the progression of PPH. The study enrolled 62 patients with PPH and 86 age- and sex-matched healthy people. The concentrations of endocan, B-type natriuretic peptide (BNP), and N-terminal prohormone of BNP (NT-pro BNP) in the serum were detected by enzyme-linked immunosorbent assay. METHODS: The Pearson correlation coefficient analyzed the correlation between endocan level and BNP and NT-pro BNP. The concentrations of IDO-dependent tryptophan metabolites in the serum were measured by high-performance liquid chromatography-tandem mass spectrometry. The diagnostic value of endocan and IDO-dependent tryptophan metabolites for PPH was evaluated by the receiver operating characteristic curve (ROC). RESULTS: Results suggested that endocan (PPH vs control: 30.56±3.61 vs 24.53±3.00 ng/mL), BNP (243.40,63.03 vs 98.60,93.35 pg/mL), NT pro-BNP (654.65,363.80 vs 141.70,158.55 pg/mL), kynurenine (1.80±0.23 vs 1.53±0.28 AU), kynurenate (5.17±0.24 vs 4.91±0.27 AU), anthranilate (5.15,2.13 vs 3.00,1.33 AU), and quinolinate (3.62±0.80 vs 2.77±0.81 AU) (all p<0.001) were upregulated in PPH patients. Moreover, Endocan levels showed strong positive correlations with both BNP (r=0.590, p<0.001) and NT pro-BNP (r=0.801, p<0.001). ROC curve showed that the combination of endocan and IDO-dependent tryptophan metabolites had diagnostic value to PPH (AUC: 0.935; 95% CI: 0.896-0.974). CONCLUSION: In short, we demonstrated that IDO-dependent tryptophan metabolites and endocan could be used as diagnostic biomarkers of PPH.