To analyze the accuracy of the defining characteristics of four respiratory nursing diagnoses (ND) in patients with COVID-19 and on oxygen therapy. This is a cross-sectional study conducted in four Brazilian public hospitals in two regions of the country. A total of 474 patients with COVID-19 receiving oxygen therapy were assessed. Latent-adjusted class analysis with random effects was used to establish the sensitivity (Se) and specificity (Sp) of the defining characteristics evaluated for each ND. Among the ND that constituted the study (impaired spontaneous ventilatory, impaired gas exchange, ineffective airway clearance, and dysfunctional ventilatory weaning response), the following defining characteristics had the highest simultaneous Se and Sp (>0.8): decrease in tidal volume, confusion, irritability, dyspnea, decreased breath sounds, orthopnea, impaired ability to cooperate and respond to coaching, and decrease in the level of consciousness. Recognizing the clinical signs that predict respiratory ND in patients affected by COVID-19 can contribute to the nurse's accurate diagnostic inference and designate the appropriate nursing interventions to achieve the desired results and avoid complications.