Sepsis is a major complication in patients with liver cirrhosis, leading to worsening of hepatic decompensation and acute on-chronic liver failure, with an associated mortality ranging between 38% and 70%. The underlying pathogenesis involves cirrhosis-associated immune dysfunction (CAID), altered gut microbiota, and intestinal permeability, leading to systemic inflammation. Assessment and management strategies for sepsis in cirrhotic patients are complex, necessitating early identification and aggressive treatment. Fluid resuscitation, vasopressor therapy, and antibiotic administration are critical components of care, but response to treatment may not be achievable in sick liver patients. Early initiation of broad-spectrum antibiotics followed by appropriate antibiotics is important to reduce bacterial resistance. Future directions include the potential of metagenomics for rapid pathogen identification and innovative therapies to address antibiotic resistance. This comprehensive review highlights the intricate relationship between liver cirrhosis and sepsis, emphasizing the need for tailored management approaches to improve patient outcomes.