Background: Prompt detection of transplant-related complications (TRC) as infections, acute graft-versus-host disease (aGVHD), microangiopathic hemolytic anemia, or veno-occlusive disease following allogeneic hematopoietic stem cell transplantation (HSCT) is essential. Patients and methods: We conducted a prospective trial on clinical significance of C-reactive protein (CRP), interleukin-6 (IL-6) and procalcitonin (PCT) serum levels in TRC. A total of 350 stem cell recipients were admitted. CRP, IL-6 and PCT were analyzed prior to conditioning and weekly until 8 wk after HSCT. TRC were recorded weekly throughout the study. Results: CRP (4.4 mg/dL vs. 12.8 mg/dL; P < 0.001), IL-6 (93 ng/mL vs. 1.138 ng/mL; P < 0.001) and PCT (0.8 ng/dL vs. 5.7 ng/dL; P < 0.001) were increased in infectious complications. Only PCT differentiated between infection and other TRC. Exclusive aGVHD did not increase CRP (4.4 mg/dL vs. 5.7 mg/dL; n.s.), IL-6 (93 ng/mL vs. 153 ng/mL; n.s.) and PCT (0.8 ng/dL vs. 0.8 ng/dL n.s.). CRP (6.1 mg/dL vs. 3.1 ing/dL; P < 0.001) and IL-6 (295 ng/mL vs. 122 ng/mL; P = 0.001) decreased during steroid therapy, but not PCT (2.3 ng/dL vs. 2.0 ng/dL; n.s.). Conclusion: Our study confirmed CRP, IL-6 and serum levels as helpful markers for TRC. PCT can differentiate infection from GVHD despite steroid therapy. Further trials are needed focusing on the identification of patients who benefit from early risk stratification.