Neuropsychiatric manifestations of COVID-19 include delirium, general malaise, headache, and psychiatric symptoms. These manifestations are related to the neuroinflammatory response to viral antigens and proinflammatory mediators/immune cells. Tetracyclines, such as minocycline, have antibacterial and anti-inflammatory properties. Saiko-keishi-to, a traditional Japanese Kampo medicine, also has anti-inflammatory properties. Given the anti-inflammatory properties of minocycline and Saiko-keishi-to, we describe two cases of COVID-19 with prolonged headaches and general malaise successfully treated with these medications.