The album's lead single, "Lose to Win", was released on January 8, 2013. On March 4, 2013, the music video for "Lose to Win" was released. On April 17, 2013, the album's second single, "Without Me" featuring Kelly Rowland and Missy Elliott was released. On July 1, 2013, the music video was released for "Without Me" featuring Kelly Rowland and Missy Elliott. On October 8, 2013, the album's third single, "Side Effects of You" was released.
Upon its release, Side Effects of You received generally favorable reviews from music critics, who complimented its progression from Barrino's earlier works. Andy Kellman from Allmusic complimented her prominent role in its production and her choice in collaborators, adding that she "has released her finest album yet". Gerrick D. Kennedy from The Los Angeles Times praised the project as "sumptuous contemporary R&B dipped in vintage rock and soul".