Doubly labeled water is gold standard for measuring total energy expenditure (TEE). Measurements using the method are sensitive to the isotope dilution space ratio (DSR). Accuracy and precision of the method might be improved if we could identify factors influencing DSR. We evaluated the potential associations of age, sex, ethnicity, anthropometry, body composition, turnover rates of the isotopes, and geographical elevation with DSR. We used univariate regression analysis to explore the relationships between the continuous variables and analysis of variance to test the relationships between the categorical variables with DSR. Subsequently, we used General Linear Modeling (GLM) and One-way ANOVA to evaluate the simultaneous associations of age, sex, ethnicity, fat-free mass (FFM) and fat mass (FM) on DSR. From 5,678 measurements complied from studies around the world with diverse ethnicity and living at various elevations, the average DSR was 1.0364 ± 0.0141 (mean ± SD). No meaningful physiological effect of any of the continuous and categorical variable on DSR was detected. GLM analysis revealed no effect of FFM and FM (P > 0.33) on DSR, but DSR decreased with age (P < 0.001) among those 60 years of age and older regardless of sex. Among the White who were younger than 60 years of age, DSR was not related to FFM and FM (P = 0.73) but was affected by both age and sex (P < 0.001). Previous estimates of age-related decline in TEE may have overestimated TEE at age 90. Validation studies on older participants are required to confirm this finding.