The "Woman Like Me" hitmakers took to the stage at the star-studded Hits Radio Live concert extravaganza as a trio, with Jesy Nelson, Perrie Edwards and Leigh-Anne Pinnock encouraging the audience to give a shout out to their bandmate.
"Unfortunately we haven't got our little Jade with us tonight but we're going to continue without her," Jesy said. "We miss her very much. Can we just give it up for Jade not being here? We love you Jade".
Representatives for the 25-year-old confirmed to Standard.co.uk that she missed the performance due to a family bereavement.
Fans took to social media to voice their concern for Jade, with one writing, "I really hope Jade is fine, I love her so much. @LittleMix." Another added, "Jade, I don't know what is going on but we mixers (fans) send you all the love and support. We love you and we hope you are doing okay. Lots of love, your mixers".
The singer's absence comes just weeks after she broke down in tears while performing the band's song "Only You", which details a couple's break-up, at an intimate Apple Music concert to promote their new album "LM5" earlier in November.
As she got to the lyric "One brick at a time we watched it fall", Jade was overcome with emotion and had to stop singing as she attempted to compose herself. Comforted by Perrie and Leigh-Anne, who stood on either side of her for the performance, Jade struggled to keep the tears at bay, as the audience touchingly encouraged her to keep going by singing the song lyrics themselves.