Siege of Perpignan ( 1542 ) The Siege of Perpignan took place in 1542 , at Perpignan ( " Spanish : Perpiñán " ) , between a larger French army commanded by Henry , Dauphin of France and the Spanish garrison at Perpignan . The Spaniards resisted until the arrival of the Spanish army under Don Fernando Álvarez de Toledo , Duke of Alba , causing the withdrawal of the French army . The siege was one of the costliest defeats of Francis I in the French offensive of 1542 . French offensive of 1542 . In June , 1541 , Francis I of France , allied with the United Duchies of Jülich - Cleves - Berg , the Ottoman Empire , Denmark and Sweden , made a show of the power at his disposal , by arriving with five armies . Francis declared war on 12 July 1542 , and the French immediately launched an offensive with the five French armies against Charles . One of them , commanded by his son Charles , Duke of Orléans went to Luxembourg . Another , led by Francis ' s eldest son , Henry , Dauphin of France , marched to Roussillon towards the frontiers of Spain . The third , commanded by Marshal Maarten van Rossum marched over Brabant , the fourth under the Duke of Vendôme to the Netherlands , and the fifth went to the Piedmont commanded by the Marshall of France Claude d ' Annebault . The result of this new offensive was another failure for Francis I . In Flanders , the army of Maarten van Rossum , supported by a German army under the Duke of Jülich - Cleves - Berg , came up against a strong Spanish - Imperial defense of Leuven and Antwerp . The Duke of Orleans attacked Luxembourg , and in the meantime , in Piedmont , the French army only managed to grab some towns due to the cunning of Claude d ' Annebault . In southern France , in Roussillon , the army commanded by Henry , Dauphin of France , consisting of 40 , 000 men , supported by the army of Marshall Claude d ' Annebault , laid siege to Perpignan , after losing valuable time which was used by the Emperor Charles to strengthen the towns of Salses , Fuenterrabía and Perpignan . Siege of Perpignan . Perpignan had been reinforced by the Emperor , which was held by several nobles of Castile and their troops , and also several hundred Spanish veteran soldiers . Henry , who thought it would be an easy conquest , encountered fierce resistance . In a clever move of the Spanish , the defenders led by the Captains Cervellón and Machichaco , attacked by surprise to the French besiegers and destroyed most of the heavy artillery with which it had already begun to damage the walls , causing a severe blow to the French army . After many hardships for the French , and without any hope that the Ottoman Empire would help them , the town was eventually relieved by the army of the Duke of Alba , forcing to the French commander , the Dauphin of France , to lift the siege , prompting the withdrawal of the French . The siege incurred a very heavy loss in dead , sick and wounded among the French ranks , becoming a resounding French failure . Consequences . When the Emperor ' s power seemed broken after the African disaster , Francis I was far from reaping the benefits of an effort that ended up being rather costly , and he couldn ' t reply with the reputation he had acquired throughout Europe . The two monarchs Charles I of Spain and Francis I of France , used up the remainder of the year to prepare new campaigns . On the French part , Frances I did everything possible to obtain military support from the Ottoman Empire , persuading Suleiman the Magnificent to return to Hungary and attack Charles of Austria ' s possessions , while the Ottoman Admiral , Hayreddin Barbarossa , attacked the Spanish and Italian coasts . In Europe , the French , under Antoine de Bourbon , Duke of Vendôme , captured Lillers in April , and Marshall Claude d ' Annebault had taken Landrecies . Wilhelm of Cleves , invaded Brabant , and the fight began in Artois and Hainaut . King Francis inexplicably halted with his army near Rheims ; in the meantime , Charles attacked Wilhelm , invading the Duchy of Julich and capturing Düren . The Duke of Orléans captured Luxembourg on 10 September , but the French conquest was useless , and Luxembourg was recaptured by the Imperial troops under the Prince of Orange . The Duke of Jülich - Cleves - Berg surrendered on 7 September , signing the Treaty of Venlo with the Emperor .