Background: Clinical prognostic factors have been reported for patients receiving systemic chemotherapy. We hypothesized that markers of tissue damage and inflammation may be prognostic. We conducted a retrospective study to evaluate the prognostic impact of serum lactate dehydrogenase (LDH) and C-reactive protein (CRP) in patients with metastatic UC. Methods: We collected data for patients with metastatic UC receiving systemic therapy and measured serum LDH and CRP at baseline before initiating therapy. The variables collected were recognized clinical prognostic factors (performance status [PS], visceral metastasis, hemoglobin, albumin) and outcomes (time to failure [TTF], overall survival [OS]). TTF was defined as time from initiation of therapy to discontinuation of agent for any reason. LDH and CRP were evaluated on a log-continuous scale. The Kaplan-Meier method was used to estimate times to events. Cox proportional hazards regression and logistic regression were used to study the association of factors with TTF and OS. All tests were 2-sided and significance was defined as p≤0.05. Results: A total of 36 patients were available with a median age of 74 years. The systemic therapy was platinum-based chemotherapy in 18 patients (50%), PD1/PD-L1 inhibitor in 8 patients (22.2%) and the remaining received other agents (taxane or investigational). Twenty-nine (80.5%) had PS 0-1, 13 (36.1%) had visceral metastasis and 16 (44.4%) had received prior platinum-based chemotherapy. A total of 31 patients were evaluable for this analysis with 5 inevaluable due to missing data or inadequate follow-up. On multivariable analyses, only CRP was associated with TTF (HR 1.55 [95% CI: 1.10, 2.20], p = 0.013) and OS (HR 1.77 [95% CI1.10, 2.85], p = 0.018). The limitations of a small dataset and retrospective analysis apply. Conclusions: In patient with advanced UC receiving systemic chemotherapy or PD1/PD-L1 inhibitors as first-line or salvage therapy, CRP was significantly prognostic for both TTF and OS, while other factors were not. Given the potentially powerful prognostic impact of CRP, investigation in larger datasets is warranted to enable better prognostic stratification.