Background: There remains limited knowledge about the immune response to SARS-COV2 vaccination in pediatric oncology patients, which is essential to provide appropriate counseling and risk adaptation in this vulnerable population. The goal of this study was to understand immunogenicity after vaccination in pediatric oncology patients and determine if certain clinical factors impacted response. Methods: After institutional review board approval, we consented patients in our clinic who had diagnosis of cancer, were 0-25 years old, and actively receiving therapy, including chemotherapy, immunotherapy, and targeted therapy. We excluded patients who were completely vaccinated prior to their cancer diagnosis. Blood samples were collected pre-vaccination, as well as 2, 6, and 8-12 weeks after vaccination. Healthy children who were fully vaccinated could also consent as controls, with samples collected up to 6 months from vaccination. Demographic data, history of COVID19 infection, and complete blood counts around time of vaccination were collected. To study immunogenicity, we measured neutralizing antibodies by enzyme-linked immunoassay (ELISA, GenScript) and interferon gamma (INFl) secretion, which measures T cell response to viral antigens, by enzyme-linked immunospot (ELISPOT, Mabtech). Results: 16 patients enrolled on study, for which 11 were evaluable along with 7 control patients. Seven patients had acute lymphoblastic leukemia, two had sarcomas, one had chronic myeloid leukemia, and one had Hodgkin lymphoma. Overall, the pediatric oncology patients had a worse immune response to vaccination compared to controls. Only one patient, who had COVID19 prior to vaccination, had similar responses to controls. Patients were divided into inadequate (n = 6) and adequate response (n = 5) based on semiquantitative analysis of immune response at 8-12 weeks post vaccination. Inadequate response was primarily seen in acute lymphoblastic leukemia patients (5 of 6 patients) and those receiving highly cytotoxic chemotherapy. Adequate response was seen in patients receiving oral therapy or chemoimmunotherapy. No patients received steroids around the time of vaccination. The inadequate response group had the lowest absolute lymphocyte counts (ALC), but ALC was variable in the adequate response group. Numbers were too small to note a difference based on age, gender, ethnicity, or type of vaccine. Conclusions: Pediatric oncology patients have a suboptimal immune response to SARS-COV2 vaccination. Malignancy type, therapy modality, and to a lesser extent, ALC at the time of vaccination, are all associated with worse immunogenicity. This study supports the need for additional doses and boosters to provide better protection against COVID19 in pediatric oncology patients.