The Byzantine civil war of 1341–47, sometimes referred to as the Second Palaiologan Civil War is a conflict that breaks out after the death of Andronikos III Palaiologos over the guardianship of his nine-year-old son and heir, John V Palaiologos.

It pits on the one hand Andronikos III's chief minister, John VI Kantakouzenos, and on the other the Empress-Dowager Anna of Savoy, the Patriarch of Constantinople John XIV Kalekas, and the megas doux Alexios Apokaukos.

The war polarizes Byzantine society along class lines, with the aristocracy backing Kantakouzenos and the lower and middle classes supporting the regency.

To a lesser extent, the conflict acquires religious overtones.

Byzantium is embroiled in the Hesychast controversy, and adherence to the mystical doctrine of Hesychasm is often equated with support for Kantakouzenos.As the chief aide and closest friend of Emperor Andronikos III, Kantakouzenos becomes regent for the underage John V upon the Emperor's death in June 1341.

While Kantakouzenos is absent from Constantinople in September the same year, a coup d'état led by Alexios Apokaukos and the Patriarch John XIV secures the support of Empress Anna and establishes a new regency.

In response, Kantakouzenos' army and supporters proclaim him co-emperor in October, cementing the rift between himself and the new regency.

The split immediately escalates into armed conflict.During the first years of the war, forces of the new regency prevail.

In the wake of several anti-aristocratic uprisings, most notably that of the Zealots in Thessalonica, a majority of the cities in Thrace and Macedonia come under regency control.

With assistance from Stephen Dushan of Serbia and Umur Beg of Aydin, Kantakouzenos successfully reverses these gains.

By 1345, despite Dushan's defection to the opposition and the withdrawal of Umur, Kantakouzenos retains the upper hand through the assistance of Orhan, ruler of the Ottoman emirate.

The June 1345 murder of megas doux Apokaukos, the regency's chief administrator, deals the regency a severe blow.

Formally crowned as emperor in Adrianople in 1346, Kantakouzenos enters Constantinople on 3 February 1347.

By agreement, he is to rule for ten years as the senior emperor and regent for John V, until the boy comes of age and rules alongside him.

Despite this apparent victory, subsequent resumption of the civil war forces John VI Kantakouzenos to abdicate and retire to become a monk in 1354.The consequences of the prolonged conflict prove disastrous for the Empire, which had regained a measure of stability under Andronikos III.

Seven years of warfare, the presence of marauding armies, social turmoil, and the advent of the Black Death devastate Byzantium and reduced it to a rump state.

The conflict also allows Dushan to conquer Albania, Epirus and most of Macedonia, where he establishes the Serbian Empire.

The Bulgarian Empire also acquires territory north of the Evros river.