Rituximab is a monoclonal antibody specific for the CD20 antigen. Clinical factors associated with thrombocytopenia after administration of rituximab have only been reported as case reports. We have analysed retrospectively the change of platelet counts following the administration of rituximab in 253 patients with non-Hodgkin lymphoma (NHL). Correlations with clinical and laboratory parameters were assessed. A mean overall decrease in platelets was observed after rituximab infusion. A downward trend in platelet count of more than 30% was observed in 7.2% of the patients. The decline was observed when rituximab was given as a single agent or in combination with chemotherapy. The risk factors to develop a decline in platelets after infusion of rituximab were pre-existent thrombocytopenia, advanced lymphoma stage, bone marrow infiltration, splenomegaly, leukemic presentation, and Burkitt lymphoma histology. In conclusion, a decline in platelet count after administration of rituximab was observed in patients with NHL, mainly those with pre-existing thrombocytopenia.