Background <p>Human albumin (HA) infusion is beneficial for the management of decompensated cirrhosis, but its mechanism remains unclear. This study aimed to evaluate the effect of HA infusion on systemic inflammation, oxidative stress, and prognosis in decompensated cirrhosis.</p> Methods <p>In a cohort study, patients with acute decompensated cirrhosis were enrolled and categorized according to HA infusion. Serum interleukin (IL)-6, IL-10, tumor necrosis factor-alpha (TNF-α), superoxide dismutase (SOD), malondialdehyde (MDA), and glutathione (GSH) levels were measured before and after treatment. We compared the one-year cumulative incidence of further decompensation between the two groups. In a meta-analysis, all relevant papers were systematically searched, and pooled using a random-effects model.</p> Results <p>In the cohort study, 55 patients were included, of whom 23 received HA infusion. HA infusion significantly reduced IL-6 (92.79 ± 144.14 vs. 66.99 ± 89.61, <i>P</i> = 0.031) and MDA (15.19 ± 8.44 vs. 11.05 ± 6.77, <i>P</i> = 0.006) levels, but increased GSH (135.76 ± 14.91 vs. 142.00 ± 19.69, <i>P</i> = 0.033) level. ∆IL-6 (-25.80 ± 64.28 vs. 1.83 ± 25.05, <i>P</i> = 0.013) and ∆TNF-α (-12.95 ± 28.91 vs. 1.82 ± 11.31, <i>P</i> = 0.037) were greater in the HA group than in the control group. One-year cumulative incidence of further decompensation was significantly lower in the HA group than in the control group (<i>P</i> = 0.036). HA infusion was an independent protective factor of further decompensation (sHR = 0.312, <i>P</i> = 0.02). In the meta-analysis, 7 papers with 450 patients were included. ∆IL-6, ∆TNF-α, and ∆MDA were greater in the HA group than in the control group, but the difference was not statistically significant.</p> Conclusions <p>HA infusion may reduce the risk of further decompensation by improving systemic inflammation and oxidative stress in decompensated cirrhosis.</p> Graphical Abstract <p></p>