Key symptoms of hypoventilation can include exertional dyspnea, orthopnea, daytime somnolence, morning headache, and anxiety. Parenchymal lung diseases, such as chronic obstructive pulmonary disease and interstitial lung disease, often include dyspnea and cough. Sleep-disordered breathing includes daytime somnolence, snoring, and fragmented sleep. Orthopnea is common in neuromuscular disorders, although weakness of the extremities or other muscle groups often precedes respiratory system muscular weakness. Hypoventilation related to neuromuscular and chest wall disorders typically begins with nocturnal hypoventilation and progresses to daytime hypercapnia. Chronic narcotic use and hypothyroidism can lead to reduced respiratory drive.

Physical examination, chest radiographic studies (CXR and possibly chest CT), and pulmonary function tests reveal most lung parenchymal and chest wall causes of hypoventilation. Measurements of maximal inspiratory and expiratory pressures or forced vital capacity can assess and monitor respiratory muscle strength. Polysomnography to assess for sleep-disordered breathing should also be considered. When pts have hypercapnia with normal pulmonary function, normal respiratory muscle strength, and normal alveolar-arterial PO₂ difference, respiratory drive abnormalities may be present, which can be revealed by polysomnography. Laboratory findings include increased PaCO₂ and often reduced PaO₂ as well. Compensatory increases in plasma bicarbonate levels and normal pH are seen in chronic hypoventilation. Eventually, pulmonary hypertension and cor pulmonale can develop. In central hypoventilation syndrome, hypercapnia worsens substantially during sleep.