To determine the role of biomarkers in the clinical management of respiratory complications (RC) in hematopoietic stem cell transplantation (HSCT) recipients, we have prospectively evaluated a cohort of 175 patients followed-up for 1 year after HSCT. To avoid misinterpretation, we have excluded both unidentified respiratory infections (RI) and mixed RI. A total of 64 RC were included. Plasma levels of C-reactive protein (CRP), procalcitonin (PCT) and proadrenomedullin (proADM) were measured at diagnosis and on day 3 and 7. Different cytokines were evaluated in serum on the first day. No HSCT recipients without RC were included as a control group. Compared with RI, non-infectious RC showed a significant increase in CRP, proADM and interleukin 6 on day 0 (P=0.005; P=0.03 and P=0.04, respectively). When only RI were considered, we observed that bacterial-fungal PI showed higher levels of CRP (P=0.02), PCT (P=0.04) and proADM (P<0.01). Persistent low levels of proADM biomarkers suggest viral infection (specificity and positive predictive value 100%). Patients dying of RC had PCT and proADM levels higher than survivors (P=0.002 and P=0.03, respectively). In HSCT recipients biomarkers increase in both infectious and non-infectious RC. They may have utility in the assessment of the severity of RC and in suspecting a viral etiology.