Early lymphocyte recovery following auto-SCT for non-Hodgkin's lymphoma (NHL) has been reported to be associated with improved outcome. The significance of early lymphocyte recovery following a stem cell transplant in NHL subtype diffuse large B-cell lymphoma (DLBCL) in the rituximab era remains unclear. Patients who underwent an auto-SCT at our institution for DLBCL during the time period 1998-2008 (n=115) were included in the study. Patient characteristics were well-balanced in both rituximab naïve and rituximab-exposed groups. Prior rituximab therapy did not affect lymphocyte recovery on day 14 or day 28. Lymphocyte recovery on day 14 and day 28 and prior rituximab had no impact on survival after auto-SCT for DLBCL, despite early benefit. Other factors such as age, stage at presentation, number of salvage regimens, mobilization procedure, conditioning regimen, pre-transplant radiation therapy and pre-transplant disease status had no impact on survival. Our data showed that the survival benefit with early lymphocyte recovery and prior rituximab seen in previous reports may be lost with longer follow-up. Prior rituximab therapy does not appear to influence the lymphocyte count at days 14 and 28 following auto-SCT. Our findings suggest that future trials should consider manipulating the immune system as a post transplant intervention to improve long-term outcome.