Prine's wife Fiona Whelan Prine had been posting updates on Twitter following his hospitalisation on 26 March. On 3 April, she wrote, "He is very ill and yet I remain hopeful that he can continue to fight this devastating virus and come home where we can care for him."

He had developed pneumonia in both lungs, and died from complications brought on by COVID-19.

The two-time Grammy winner released 18 studio albums throughout his career, his most recent being 2018's The Tree of Forgiveness.

Bruce Springsteen, Sheryl Crow, and many other Americana/country/folk musicians have been paying tribute on socials.