In his letter of resignation to Speaker John Boehner, Radel said his resignation would be effective at 6:30 p.m. EST, on Monday.
"Regardless of some personal struggles in 2013, this year has already been tremendously positive as I focus on my health, family and faith," the letter said. "Unfortunately, some of my struggles had serious consequences. While I have dealt with those issues on a personal level, it is my belief that professionally I cannot fully and effectively serve as a United States Representative to the place I love and call home, Southwest Florida."
He also sent letters of resignation to Florida Gov. Rick Scott and Florida's Department of State.
The freshman congressman's announcement came weeks after he returned to Capitol Hill following his arrest for buying cocaine, the Hill reported.
After finishing his rehabilitation at a Florida clinic, Radel vowed to work hard upon his return to Congress to rebuild the trust he lost. But he faced pressure to resign from both Republicans and Democrats in Florida.
Earlier in January, former Florida state Rep. Paige Kreegel, a Republican, became the first person to announce a primary challenge against Radel, the Hill said. Kreegel lost to Radel in the 2012 primary race.
Republican National Committee Chairman Reince Priebus told MSNBC Radel "absolutely" did the right thing by resigning.
Scott will set the dates for a special election.
Radel did not indicate his next steps, saying, "I hope to contribute what I can to better our country in the years to come."