Abstract After autologous stem cell transplant (AuSCT), patients with multiple myeloma (MM) may receive lenalidomide maintenance therapy. This longitudinal study examined patient-reported symptom burden during the 3-9 months post-AuSCT and its association with maintenance therapy and circulating inflammatory markers. Fifty-one MM patients rated symptom severity weekly using the MD Anderson Symptom Inventory MM module. When possible, blood for inflammatory marker assay was drawn at enrollment. Trajectory analysis identified clusters of patients who consistently reported higher or lower symptom severity. Although disease was relatively stable 3-9 months post-AuSCT, patients were not symptom-free: 35% were in the high-symptom group. Fatigue, pain, numbness/tingling, bone aches, and muscle weakness were the most-severe symptoms. Controlled for clinical variables, elevated baseline TNF-α predicted high-symptom group membership (p = 0.014). Maintenance therapy and tumor response were not related to high symptom burden. Associations between Inflammation and symptom burden in this exploratory study warrant further confirmatory study.