Glucose-fructose ingestion increases glucose and lactate oxidation during exercise. We hypothesized that training with glucose-fructose would induce key adaptations in lactate metabolism. Two groups of eight sedentary males were endurance-trained for three weeks while ingesting either glucose-fructose (GF) or water (C). Effects of glucose-fructose on lactate appearance, oxidation, and clearance were measured at rest and during exercise, pre-training, and post-training. Pre-training, resting lactate appearance was 3.6 ± 0.5 vs. 3.6 ± 0.4 mg·kg javax.xml.bind.JAXBElement@1ca983d4 ·min javax.xml.bind.JAXBElement@7b9c8542 in GF and C, and was increased to 11.2 ± 1.4 vs. 8.8 ± 0.7 mg·kg javax.xml.bind.JAXBElement@1db23ebc ·min javax.xml.bind.JAXBElement@7d82d9ab by exercise (Exercise: javax.xml.bind.JAXBElement@2d6552ec < 0.01). Lactate oxidation represented 20.6% ± 1.0% and 17.5% ± 1.7% of lactate appearance at rest, and 86.3% ± 3.8% and 86.8% ± 6.6% during exercise (Exercise: javax.xml.bind.JAXBElement@324c6497 < 0.01) in GF and C, respectively. Training with GF increased resting lactate appearance and oxidation (Training × Intervention: both javax.xml.bind.JAXBElement@3e07fbbc < 0.05), but not during exercise (Training × Intervention: both javax.xml.bind.JAXBElement@55a33256 > 0.05). Training with GF and C had similar effects to increase lactate clearance during exercise (+15.5 ± 9.2 and +10.1 ± 5.9 mL·kg javax.xml.bind.JAXBElement@52d6e83c ·min javax.xml.bind.JAXBElement@3ef562d ; Training: javax.xml.bind.JAXBElement@23497f7 < 0.01; Training × Intervention: javax.xml.bind.JAXBElement@4ec92465 = 0.97). The findings of this study show that in sedentary participants, glucose-fructose ingestion leads to high systemic lactate appearance, most of which is disposed non-oxidatively at rest and is oxidized during exercise. Training with or without glucose-fructose increases lactate clearance, without altering lactate appearance and oxidation during exercise.