The phrenic nerve arises from the third, fourth, and fifth cervical spinal nerves (C3-C5). It provides motor innervation to the diaphragm and is thus responsible for the act of breathing. In addition, it provides sensory innervation for many components of the mediastinum and pleura, as well as the upper abdomen, especially the liver and gall bladder. Pain arising from structures served by the phrenic nerve is often "referred" to other somatic regions served by spinal nerves C3-C5. For instance, angina pectoris classically is felt both in the chest and in the left arm. Likewise, a liver abscess close to the diaphragm will be felt in the right shoulder.

Both phrenic nerves run from C3, C4 and C5 along the anterior scalene muscle deep to the carotid sheath. The right phrenic nerve passes over the right brachiocephalic artery, the subclavian vein, and the superior vena cava and then crosses the root of the right lung and then leaves the thorax by passing through the vena cava hiatus opening in the diaphragm at the level of T10. The right phrenic nerve passes over the right atrium. The left phrenic nerve passes over the left ventricle and pierces the diaphragm separately.

Both these nerves supply motor fibres to the diaphragm and sensory fibres to the fibrous pericardium, mediastinal pleura and diaphragmatic peritoneum.

Irritation of the phrenic nerve leads to the Hiccup Reflex, which is due to spasms of the diaphram pushing air that hits the closed folds of the glottis.

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Peripheral nervous system