Among the neurological manifestations associated with coronavirus disease 2019 (COVID-19), neuropathies are rare. They have been associated with prolonged prostration and metabolic failure in a seriously ill patient. We present a case series of four Mexican patients diagnosed with diaphragmatic dysfunction due to phrenic neuropathy during acute COVID-19, documented by conduction velocities of the phrenic nerves. Blood tests, chest computed tomography (CT), and nerve conduction velocities of the phrenic nerves were performed. COVID-19 patients with phrenic nerve neuropathy represent a therapeutic challenge since they have high oxygen requirements due to the malfunction of ventilatory mechanics secondary to neuromuscular damage, as well as the damage that pneumonia generates in lung tissue. We confirm and extend the neurological manifestations of COVID-19, the impact on the neuromuscular dysfunction of the diaphragm, and its consequences such as the difficulty of weaning from mechanical ventilation.