Objective: Melanoma is an aggressive form of skin cancer. The growing incidence of cancer has been associated with systemic inflammation, and novel indicators such as the pan-immune inflammation value (PIV) and Systemic Inflammation Response Index (SIRI) may be used as prognostic markers for cancer. In this context, the prognostic significance of SIRI and PIV was evaluated in patients with metastatic melanoma. Material and Methods: A retrospective analysis involving 58 patients diagnosed with metastatic melanoma at Marmara University was conducted. SIRI and PIV were calculated using baseline neutrophil, monocyte, platelet, and lymphocyte counts. Results: Patients with SIRI≥1.5 had significantly shorter progression-free survival (PFS) (mean 29.7 vs. 55.6 months, p=0.022) and overall survival (OS) (mean 38.9 vs. 78.8 months, p=0.006) compared to those with SIRI<1.5. Similarly, PIV≥390 was associated with shorter PFS (mean 28.3 vs. 57.4 months, p=0.007) and OS (mean 39.2 vs. 78.8 months, p=0.007). The multivariate analysis, revealed SIRI as an independent prognostic factor for OS (HR: 2.2; 95% CI: 1.16-4.26, p=0.01), while PIV did not reach significance (HR: 1.2; 95% CI: 0.25-5.97, p=0.78). Conclusion: SIRI is an important independent prognostic marker for OS in patients with metastatic melanoma and should, therefore, be incorporated into clinical practice for risk stratification. Although PIV is associated with survival outcomes of patients, as revealed in the univariate analysis, it did not reach significance in the multivariate analysis. Further studies are necessary to confirm these findings, increase the prognostic significance of SIRI, and evaluate the efficacy of using SIRI in combination with other biomarkers.