In 1602, shortly before his death, he also signed an agreement with Philip III of Spain, who granted him a pension that could also be passed on to his heirs.

In the beginning of 1602, an epidemic of pestilential fever called 'burraschetta' broke out in Mirandola, causing over 200 people to die within three months.

The Mirandola rulers, who in the meantime had taken refuge in Reggio Emilia, then asked for divine grace, supplicating the holy image of the Virgin placed on the northern gate of the walls.

[2] While the epidemic seemed to have ended, in April, Federico II commissioned the construction of the Oratory of the Blessed Virgin of the Gate (today known as the Church of the Madonnina) by grace received.

However, on 20 April his wife Princess Ippolita d'Este fell victim to the same strange flu, dying on 1 May at the age of just 36.