On January 8, 2019, Harris was reportedly taken to a hospital in Chicago after tweeting that she was going to commit suicide. In a tweet posted the next day, Harris wrote "I've been fighting with depression for the longest. Sorry that I did it public last night but I'm ok. I went to the hospital & I'm finally getting the help that I need to get through, be happy, & deliver great music. Thanks for all the prayers but please don't worry bout me."
On January 11, 2019, the single Squidward Nose was released, and on February 21, 2019, a music video for the song featuring John Early premiered. On April 17, 2019, Harris released a remix of Lil Nas X's song "Old Town Road" titled "Old Town Hoe". It was released exclusively on her YouTube channel. A music video was released the following day.
In September 2019, Harris announced her retirement in an Instagram live video, stating, "This live is going to be the last video that y'all [will] see of me". She stated that she would no longer be releasing music to the public and that she would be removing her music from all streaming platforms. She stated that she was disturbed to see children in videos and young people at her shows singing along to her explicit songs, felt she was "corrupting the youth" with her raunchy songs. and said "I want to go to heaven after this. I don’t want to go to hell”. Harris also told fans that she has a "very bad gambling addiction" and that she had lost $700,000 at a casino in September 2018. She concluded the video by thanking her fans for their support and for saving her and her family from homelessness which they experienced prior to Harris' career in music.
On November 7, 2019, CupcakKe came out of retirement after a 40-day absence on all social media platforms with a tweet; "Jesus fasted for 40 days & so did I...... Nov 16th". On March 6, 2020, CupcakKe released a new single, "Lawd Jesus." CupcakKe uploaded her first video to YouTube since her previous deletion of all videos on her channel in 2019 with the double video for singles "Grilling Niggas" and "Lawd Jesus", released on May 13, 2020.