The song will debut on the U.S. iTunes store at midnight. "Hold It Against Me" is the official lead single from her upcoming seventh studio album, which is set to hit stores in March, her record company, Jive, said in a statement.
Spears last released new music in 2009. "Hold It Against Me" was produced by Spears' long-time collaborators Max Martin and Dr. Luke. Fans will be able to purchase it on iTunes until January 18.
On December 2, Spears' 29th birthday, the singer wrote on her official Twitter page, "I'm almost done with my new album and it will be coming out this March. I AM IN L-O-V-E WITH IT!"
Spears has in recent years rebuilt an image many thought was forever tarnished by rehab stints for substance abuse, excessive partying and a now-infamous head-shaving incident from 2007.
Her comeback is on a steady track with appearances on 'Glee', a successful tour and an endorsement deal with Elizabeth Arden, putting her at No. 3 on Forbes' list of Hollywood's highest-earning women with $64 million.