Objective To explore the association between serum soluble leptin receptor (sOB-R), Tenascin-C and life events, suicidal ideation in patients with severe depression. Methods A total of 83 patients (case group) with severe depression admitted to our hospital were divided into suicidal ideation group (n=37) and non-suicidal ideation group (n=46) according to presence or absence of suicidal ideation. 60 healthy volunteers who underwent physical examination during the same period were selected as control group. Serum sOB-R and tenascin-C levels were measured using enzyme-linked immunosorbent assay, and life events scale (LES) was used to assess the scores of each group. Pearson product moment correlation analysis was used to analyze the association between serum sOB-R, tenascin-C and life event scores. Multivariate logistic regression analysis was used to analyze the influence of serum sOB-R, tenascin-C on suicidal ideation. The receptor operating characteristic (ROC) curve was drawn to evaluate the predictive value of serum sOB-R, tenascin-C for suicidal ideation. Results Serum sOB-R level in case group was lower than that in control group, while serum tenascin-C level was higher than that in control group (P<0.05). The amount of negative event stimulation and total score of life event stress were higher than those in control, while the amount of positive events stimulation was lower than that of control group (P<0.05). The Pearson product moment correlation analysis results showed that serum sOB-R was negative association with the amount of negative event stimulation in patients with severe depression (r=-0.649, P<0.05), and tenascin-C was positively associated with the amount of negative event stimulation (r=0.721, P<0.05). The results of multivariate logistic regression showed that woman, a history of attempted suicide, anxiety, elevated tenascin-C, and an increase in amount of negative event stimulation were independent risk factors for suicidal ideation (OR=1.384, 1.338, 1.481, 1.372, 1.215; P<0.05), sOB-R was a protective factor for suicidal ideation (OR=0.716, P<0.05). sOB-R, tenascin-C have certain predictive value for suicidal ideation, with AUC of 0.805, 0.816, respectively. The combined prediction value is higher (Z=4.018, 3.692; P<0.05), with AUC of 0.902, sensitivity and specificity of 0.923 and 0.867, respectively. Conclusion Patients with severe depression have a decrease in serum sOB-R and an increase in tenascin-C, which are closely related to life event scores and can effectively predict the risk of suicidal ideation