"Kay meant everything to us, and we were honored to share her with the people of North Carolina whom she cared for and fought for so passionately as an elected official," the statement read. "Most of all, we already miss her humor and spirit as the hub of our family, a role she loved more than anything. Nobody could light up a room and make people feel welcome like Kay."
Hagan died of encephalitis, or brain inflammation, caused by Powassan virus, a rare virus spread from ticks to humans, her former Senate spokeswoman Sadie Weiner said.
She was elected in 2008 and served from 2009 to 2015 before she was defeated by Republican Thom Tillis. She also spent a decade serving in the North Carolina General Assembly.
Gov. Roy Cooper described Hagan as a fierce advocate for the state and an inspiration for young girls to enter public service.
"She made it a mission to inspire young people – especially young girls – to enter public service, and she served as a role model to so many," he said in a statement. "North Carolina is mourning one of our best today."
Hagan was born in Shelby, North Carolina. During her time in the Senate, she cast one of the deciding votes for the Affordable Care Act. She served on the Armed Services Committee and helped prevent cuts to tuition assistance programs for veterans.
In a statement, former President Barack Obama said he appreciated her "reasoned, pragmatic voice, whether we were working together to pass the Affordable Care Act, reform Wall Street, support working families or just make Americans' lives a little better."
He added: "Her record is one all public servants would do well to follow, and her perspective is one we'll sorely miss."
Former Vice President and 2020 Democratic presidential candidate Joe Biden also released a statement, calling Hagan "a courageous soul who lived every day of her too-short life with incredible dignity and character, even as the days became more difficult physically."
In June, Hagan made a rare public appearance at a groundbreaking ceremony for an airport where she helped gain funding.
She helped break ground at Piedmont Triad International Airport's new air traffic control tower. The airport executive director said at the time that Hagan visited the airport during her time as a senator and helped alert others in Washington to the need for a new tower.
In addition to her husband, Hagan is survived by three children: Jeanette Hagan, Tilden Hagan and Carrie Hagan Stewart.
– The Associated Press contributed to this report.