Accurate prediction of the recovery of Disorders of Consciousness (DoC) is of paramount significance for clinicians and families. Serum total bilirubin (TBIL) formed by activation of heme oxygenase 2, is associated with incidence and prognosis of cardiovascular and cerebrovascular diseases. However, studies that based TBIL and DoC are limited. The study attempted to examine the association between serum TBIL levels and prognosis in patients with DoC. One hundred and sixty-eight patients with DoC in the Second hospital of Shandong University from June 2021 to June 2023 were recruited. The clinical characteristics and venous blood samples were collected within 24 h after admission. The diagnosis of DoC was determined by two skilled investigators employing various behavioral evaluations along the coma recovery scale-revised (CRS-R) and the investigators conducted follow-up assessments of diagnosis at 1, 3, and 6 months after admission. For statistical analysis, we categorized patients with an improvement in clinical diagnosis from study entry as having a "good outcome". In total, 139 individuals enrolled in the study. The median TBIL level was 8.2 μmol/L. Good recovery of DoC at 1, 3, and 6 months occurred in 25 (18.0%), 41 (29.5%), and 56 (40.3%) patients, respectively. After full adjustment, a significant association was found between TBIL levels and the prognosis of DoC at 1, 3, and 6 months. When TBIL levels were analyzed as categorical variables, an increasing trend in the tertiles of TBIL levels demonstrated a significant positive association with the recovery of DoC at 1, 3, and 6 months. Stratified analysis revealed that the association between serum TBIL levels and the recovery of DoC remained consistent across different sub-populations. A high serum TBIL level is associated with an improved likelihood of recovery of DoC. Additional research is required to elucidate the underlying pathophysiological causal association between TBIL levels and DoC.