Objective To assess the impact of prior COVID-19 infection on clinical outcomes in terms of engraftment, treatment emergent complications, and immune reconstitution in multiple myeloma (MM) patients after autologous hematopoietic stem cell transplantation (auto-HSCT). Methods Data of MM patients who underwent auto-HSCT from July 1, 2022, to July 31, 2023, in Ruijin Hospital, Shanghai Jiao Tong University School of Medicine were retrospectively analyzed. The clinical indices including engraftment time, transplant-related infection, engraftment syndrome, immunoglobulin reconstitution, circulating lymphocytes composition, and short-term efficacy were compared in the two cohorts who had or had not been infected by COVID-19 prior to auto-HSCT. Results Sixty-three patients were included. Thirty-two recovered from COVID-19 before auto-HSCT and the remaining 31 did not show evidence of COVID-19 infection. No differences were observed across the two groups in the rates of infections, neutrophil engraftment, platelet engraftment, as well as the incidence of engraftment syndrome. Preceding auto-HSCT, the numbers of CD3⁺T, CD3⁺CD8⁺T and CD19⁺B lymphocytes in patients recovered from COVID-19 were significantly higher than those in COVID-19-free group (P<0.05); however, such a disparity was not present after auto-HSCT. At day 8 post-infusion, interferon(IFN)-γ level of COVID-19 group was higher as compared with that of non-infected group (P=0.011).The rate of polyclonal immunoglobulins recovery in COVID-19-affected cohort was 3.1%, which was lower than that in non-infected patients three months post auto-HSCT (P=0.026), while there was no difference in depth of therapeutic response between the two groups. Conclusions The data indicates that auto-HSCT can be safely administered in MM patients who completely recovered from COVID-19, but their immunoglobulins reconstitution was relatively delayed upon adoptive transfer. Timely and routine intravenous immunoglobin supplements are recommended for minimizing the risk of infection.