We undertook a retrospective analysis of a cohort of 67 patients with multiple myeloma who had received an autologous haematopoietic SCT (HSCT) following high-dose melphalan to explore the impact of mucositis on the systemic inflammatory response. A homogenous group of 16 patients without a documented infection and a group of 30 patients with bacteraemia were identified for whom complete data on neutropenia, an inflammatory response, infectious complications and mucositis were available. All patients showed a similar course of events with an inflammatory response coinciding with the occurrence of significant mucositis, regardless of the presence or absence of infection. The only differences between the two groups were significantly higher maximum C-reactive protein (CRP) levels and lower citrulline levels for patients with bacteraemia, suggesting a causative role for mucositis in the occurrence of bacteraemia. Statistical analysis showed a significant association over time between citrulline levels, to a lesser extent bacteraemia, but not neutropenia, and the inflammatory response measured by CRP. These data suggest that the inflammatory response after conditioning for a HSCT is the result of the chemotherapy-induced mucositis and independent of neutropenia. Though primary inflammation appeared due to mucositis, infections resulting from mucosal barrier injury and neutropenia aggravated the inflammatory response.