Autologous stem cell transplantation (ASCT) is challenged by side effects that may be propagated by chemotherapy-induced mucositis resulting in bacterial translocation and systemic inflammation. Since gastrointestinal damage appear as an early event in this cascade of reactions, we hypothesized that markers reflecting damage to the intestinal barrier could serve as early predictive markers of toxicity. Glucagon-like peptide-1 (GLP-1), a well-known regulator of blood glucose, has been found to promote intestinal growth and repair in animal studies. We investigated fasting GLP-1 plasma levels in 66 adults undergoing ASCT for lymphoma and multiple myeloma. GLP-1 increased significantly after chemotherapy reaching peak levels at day +7 post-transplant (median (IQR): 8 (4-12) before conditioning vs. 10 (6-17) pmol/L at day +7, P=0.007). The magnitude of the GLP-1 increase was related to the intensity of conditioning. GLP-1 at the day of transplantation (day 0) was positively associated with peak C-reactive protein (CRP) levels (46 mg/L per GLP-1 doubling, P<0.001) and increase in days with fever (32% per GLP-1 doubling, P=0.0058). Patients with GLP-1 above the median at day 0 had higher CRP levels from day +3 to day +10 post-transplant than patients with lower GLP-1 (P≤0.041) with peak values of 238 vs. 129 mg/L, respectively. This study, which represents the first clinical investigation of fasting GLP-1 in relation to high-dose chemotherapy, provides evidence that GLP-1 plays a role in regulation of mucosal defenses. Fasting GLP-1 levels may serve as an early predictor of systemic inflammation and fever in patients receiving high-dose chemotherapy.