Objective: The majority of zoo African elephants exhibit abnormal reproductive cycles, but it is unclear why. Acyclicity has been positively associated with body condition scores. The objective of this study was to measure body composition and examine the relationship between adiposity and cyclicity status, mediated by glucose, insulin, leptin, and inflammation. Methods: Body composition was assessed by deuterium dilution in 22 African elephants. Each elephant was weighed and given deuterated water orally (0.05 mL/kg), and blood was collected from the ear prior to and five times after deuterium administration. Glucose, insulin, leptin, and proinflammatory biomarker concentrations in serum were determined. Results: Body fat percentage ranged from 5.24% to 15.97%. Fat adjusted for fat free mass (FFM) and age was not significantly associated with cyclicity status (P = 0.332). Age was the strongest predictor of cyclicity status (P = 0.040). Fat was correlated with weight (ρ = 0.455, P = 0.044) and when adjusted for FFM with circulating glucose (ρ = 0.520, P = 0.022) and showed a trend for association with leptin (unadjusted: ρ = 0.384, P = 0.095; adjusted for FFM: ρ = 0.403, P = 0.087). Conclusions: Deuterium dilution appears to be an available technique to measure body composition in African elephants. In this sample, fat was not associated with cyclicity status, and age may be more important to cyclicity status.