Abstract Background and Aims The liver plays a key role in the storage, metabolism and homeostasis of fat-soluble vitamins. We investigated the relation of Vitamin(Vit)A/D/E serum levels with severity of liver disease and portal hypertension (PHT). Methods VitA/D/E serum levels were assessed in 234 patients with advanced chronic liver disease (ACLD, i.e. hepatic venous pressure gradient [HVPG] ≥ 6 mmHg). Patients with hepatocellular carcinoma, pre-/post-hepatic PHT, TIPS or liver transplantation were excluded. Results Most patients were male (n = 153; 65%) with a median age of 57.6 (49.7–64.5) years. Thirty-two (14%) patients had HVPG 6–9 mmHg, 66 (28%) 10-15 mmHg, and 136 (58%) ≥ 16 mmHg, respectively. VitD deficiency (25-OH-vitamin-D <50 nmol/L) was found in 133 (57%) with higher prevalence in Child-Turcotte-Pugh (CTP)-C: 85% vs. B: 66% vs. A: 47% (p < 0.001). VitD levels displayed significant but weak correlations with hepatic dysfunction and PHT. VitE levels were normal in 227 (97%) patients and displayed no relevant association with hepatic dysfunction or PHT. Only 63 (27%) patients had normal (>1.05 µmol/L) VitA levels, while 58 (25%) had mild (0.70–1.04 µmol/L), 71 (30%) moderate (0.35–0.69 µmol/L), and 42(18%) severe(<0.35 µmol/L) VitA deficiency. VitA correlated with HVPG (Rho = −0.409), CTP score (Rho = −0.646), and serum bile acid levels (Rho = −0.531; all p < 0.001). The prevalence of decompensated ACLD (dACLD) continuously increased with severity of VitA deficiency (no: 40% vs. mild: 51% vs. moderate: 67% vs. severe: 91% had dACLD; p < 0.001). CTP score (per point; OR 2.46; 95%CI 1.80–3.37; p <0.001), age (per year; OR 0.95; 95%CI 0.92–0.98; p = 0.001) and elevated bile acid levels(>10 µmol/L; OR 3.62; 95%CI 1.61–8.14; p = 0.002) were independently associated with VitA deficiency. Conclusion VitA and VitD but not VitE deficiencies are highly prevalent in ACLD. VitA deficiency strongly correlates with hepatic dysfunction, PHT and bile acid levels and is associated with decompensated ACLD. Trial registration number NCT03267615.