Background: Blood-based-inflammation-markers (BBIM) and Body Mass Index (BMI) have been associated with overall survival (OS) in a number of cancers. Inflammation and obesity have biological interactions. We evaluated the role of Neutrophil-to-Lymphocyte-Ratio (NLR), Platelet-to-Lymphocyte-Ratio (PLR) and Systemic-Inflammation-Index (SII) in conjunction with BMI as predictors of OS in localized/locally-advanced-esophageal cancer (LEC/LAEC). Methods: LEC/LAEC patients treated from 2006-2014 had the following variables analyzed both as continuous and categorical: BMI (low <25 kg/m², high ≥25 kg/m²), NLR (low <4, high ≥4), PLR (low <232, high ≥232), and SII (low <1375, high ≥1375), with OS. Univariate (UVA) and Multivariate analysis (MVA) were analyzed using Cox regression (adjusted hazard ratios, aHR; 95% Confidence Intervals, CI). MVA models of OS were built, assessing different categorical combinations of BBIM factors with and without BMI. Results: Of 411 pts, 79% were males, median age was 63.5 years, 67% were adenocarcinomas; Stage I/II/III: 14%, 28%, 59%; Median BMI was 26.5kg/m² and BMI distribution was: 3% underweight, 40% normal weight, 37% overweight and 20% obese. After a median follow-up of 87 months, 204 pts recurred, and 257 died. In MVA, BMI alone had no impact on OS (aHR 0.89, CI 0.7-1.1, p=0.15); individually as continuous variables, higher SII (p=0.03) and higher NLR (p=0.006) were inversely associated with OS whereas higher PLR was not (p=0.10). In an MVA of categorical combinations of BMI and BBIM on OS, patients in the high-BMI/low-PLR group were at lower risk of death when compared to all other groups (aHR=0.65, 95%CI:0.5-0.8, p=0.007). Similar non-statistically significant trends were shown when SII and NLR were individually combined with BMI (aHR=0.77, 95%CI:0.6-1.0, p=0.09; aHR=0.74, 95%CI:0.5-1.0, p=0.05, respectively). Conclusions: Our results suggest that in LEC/LAEC pts, high BMI and low PLR together are associated with improved OS when compared to pts with low BMI and/or high PLR. NLR and SII alone were associated with OS. Further studies evaluating the underlying mechanisms of BBMI, in particular PLR and inflammation/obesity are warranted.