Nicholas Francis was named abbot in commendam – a lucrative sinecure – of several abbeys and was sent on several embassies by his brother, Charles IV, Duke of Lorraine, and by Louis XIII of France.

He wrote to Pope Urban VIII, 4 March 1634, resigning as cardinal to marry his cousin Claude of Lorraine, the second daughter of Henry II, on 17–18 February.

On 8 March 1634, the pope declared him in nullo e sacris ordinis constitutum, depriving him of the title of cardinal and the diocese of Toul.

Immediately following Nicholas's accession to the dukedom, the French invaded the duchy and forced the new duke to sign a treaty recognizing their right to occupy it.

In April 1634, Nicholas himself fled into exile, and soon after abdicated himself, returning the claim to the duchy to his older brother, Charles.