Background and Methods: There is an added level of complexity in the management of head and neck cancer patients with underlying immunosuppressive disorders during the COVID-19 pandemic. Head and neck oncologists are tasked with balancing the dual risks of cancer progression in the setting of impaired tumor immunity and increased susceptibility to life-threatening complications from exposure to viral infection for patients and providers. Through two cases of immunocompromised patients with newly diagnosed head and neck malignancies, we aim to provide guidance to clinicians struggling with how to best counsel and manage this unique subset of patients under these difficult circumstances. Results: After careful consideration of the options, we took different approaches in the care of these two patients. Conclusions: Ultimately, there is no uniform set of rules to apply to this heterogeneous group of immune-compromised patients. We provide some general principles to help guide patient management during the current pandemic.