Background: Community-acquired pneumonia is an established independent risk factor for atherosclerosis, yet the molecular mechanisms translating acute pulmonary infection into chronic vascular pathology remains poorly understood. Methods: We considered sphingolipids as a potential molecular mediator between acute infection and chronic coronary artery disease phenotypes. For this purpose, we measured sphingolipids with LC-MS/MS in three cohorts: (1) acute pneumonia patients (N=377), (2) patients with stable and unstable coronary artery disease (N=526) and (3) healthy controls (N=400). We identified features associated with pneumonia and coronary artery disease and probed these features for causality using Mendelian randomization (MR). Results: From 43 analyzed features, 17 were associated with pneumonia and cardiovascular endpoints with concordant effect direction. Features included pro-inflammatory ceramides and sphingosine-1-phosphate (S1P). Subsequent causal inference analyses identified C18:0 sphingomyelin (SM 18:0) as a statistically significant causal factor for CAD (β = 0.62; FDR q = 7.35 × 10⁻¹⁰). Follow-up MR and mediation analyses resolved potential pleiotropy by establishing a causal pathway flowing from LDL-cholesterol (LDL-C) to SM 18:0, revealing that SM 18:0 partly mediates the LDL-C-driven risk for CAD. Of note, a divergent pattern emerged within the pneumonia cohort: patients exhibited upregulated SM 18:0 despite downregulated total cholesterol. This discrepancy implies that during acute infection, SM 18:0 is upregulated via distinct, cholesterol-independent inflammatory mechanisms. Conclusion: We propose inflammation-induced accumulation of SM 18:0 as a causal mediator linking the acute systemic stress of pneumonia to the long-term progression of cardiovascular disease.