BACKGROUND: Hyperlipidemia contributes to immune-inflammatory imbalance and poor outcomes in critical illness. The pan-immune-inflammation value (PIV), derived from neutrophil, monocyte, platelet, and lymphocyte counts, may capture this burden, but its prognostic value in critically ill patients with hyperlipidemia is unclear. METHODS: We conducted a retrospective cohort study using MIMIC-IV (v3.1). Adults with a first ICU admission and ICD-coded hyperlipidemia, with complete blood counts within 24 h, were included. lnPIV (ln-transformed PIV) was analyzed as continuous and categorical (quartiles) exposures. Primary outcomes were 28-, 90-, and 180-day mortality; secondary outcomes included ICU and in-hospital mortality, acute kidney injury (AKI), and delirium. Survival, Cox regression, restricted cubic spline (RCS), and ROC analyses were applied. RESULTS: Among 12,408 patients (mean age 70 years; 38.6% female), 1,309 died in hospital. Higher lnPIV was independently associated with 28-day (HR = 1.14, 95% CI: 1.10-1.18), 90-day (HR = 1.15, 95% CI: 1.11-1.18), and 180-day mortality (HR = 1.13, 95% CI: 1.10-1.16; all P < 0.001). RCS analysis identified a threshold at PIV ≈ 172, above which mortality risk increased sharply. The highest quartile had significantly greater in-hospital mortality risk (OR = 1.85, 95% CI: 1.50-2.29). Adding PIV to the SOFA score significantly improved discrimination (AUC increased from 0.55 to 0.67, P < 0.001) and provided positive net benefit across clinically relevant threshold probabilities. lnPIV was also associated with AKI and delirium. CONCLUSION: Elevated PIV is independently associated with mortality and adverse outcomes in critically ill patients with hyperlipidemia. As a simple and readily available composite marker, PIV may complement existing risk scores for early risk stratification in this vulnerable population.