Respiratory failure can manifest suddenly or gradually, characterized by a rapid decline in PaO2 and a rapid rise in PaCO2. This situation indicates a severe respiratory problem that may quickly become a life-threatening emergency. One of the early signs of hypoxemic Acute Respiratory Failure (ARF) is a change in mental status due to the brain's sensitivity to oxygen levels and changes in acid-base balance. Symptoms such as restlessness, confusion, and agitation suggest inadequate oxygen delivery to the brain. In contrast, a morning headache and a low respiratory rate with decreased consciousness may indicate problems with carbon dioxide removal.

Tachycardia, tachypnea, pallor, and a slight increase in the work of breathing (WOB) are early indications of ARF. These signs reflect the body's efforts to compensate for the diminished oxygen delivery and increased carbon dioxide levels. Cyanosis, often linked with hypoxemia, is an unreliable sign and usually appears late in ARF, at a deoxygenated hemoglobin concentration of about 5g/dL. However, observing the patient's position can provide insights into their WOB; mild respiratory distress allows for lying down, moderate distress leads to a preference for sitting, and severe distress necessitates an upright or tripod position to ease breathing. In the tripod position, patients sit with their arms supported on an overbed table or their knees, which helps reduce the WOB by changing chest dimensions and thoracic pressure.

Patients with ARF may show a rapid, shallow breathing pattern or a slower respiratory rate, leading to hypoxemia and inadequate carbon dioxide removal. A transition from rapid to slower breathing in a distressed patient signals severe respiratory muscle fatigue, raising the risk of respiratory arrest. The ability to speak varies with the severity of dyspnea; patients struggling to breathe can often talk only a few words at a time between breaths. Signs of respiratory distress include pursed-lip breathing, retraction of the intercostal spaces or supraclavicular areas, and the use of accessory muscles.

Severe distress may result in paradoxical breathing, where the chest moves inward during inhalation and outward during exhalation, opposite the usual pattern. This abnormal breathing pattern is a critical sign of an advanced stage of respiratory distress.