Background: Previous studies have reported differences in aerobic exercise capacity, expressed as peak oxygen uptake (VO_2peak), between people with and without cystic fibrosis (CF) related diabetes (CFRD). However, none of the studies controlled for the potential influence of physical activity on VO_2peak. We investigated associations between CFRD and VO_2peak following rigorous control for confounders including objectively measured physical activity. Methods: Baseline data from the international multicenter trial ACTIVATE-CF with participants ≥12 years performing up to 4 h per week of vigorous physical activity were used for this project. Multivariable models were computed to study associations between CFRD and VO_2peak (mL.min⁻¹) adjusting for a set of pre-defined covariates: age, sex, weight, forced expiratory volume in 1 s (FEV₁), breathing reserve index, Pseudomonas aeruginosa infection, and physical activity (aerobic step counts from pedometry). Variables were selected based on their potential confounding effect on the association between VO_2peak and CFRD. Results: Among 117 randomized individuals, 103 (52% female) had a maximal exercise test and were included in the analysis. Participants with (n = 19) and without (n = 84) CFRD did not differ in FEV₁, physical activity, nutritional status, and other clinical characteristics. There were also no differences in VO_2peak (mL.min⁻¹ or mL.kg⁻¹.min⁻¹ or% predicted). In the final multivariable model, all pre-defined covariates were significant predictors of VO_2peak (mL.min⁻¹), however CFRD [coefficient 82.1, 95% CI -69.5 to 233.8, p = 0.28] was not. Conclusions: This study suggests no meaningful differences in VO_2peak between people with and without CFRD given comparable levels of physical activity.