The reality TV star, originally from Northwood in London, checked into a private hospital last month after her eating disorder worsened in lockdown.
It came after her friends managed to raise more than £65,500 via a fundraising page to start paying for life-saving care.
However, her passing was confirmed in a statement today on her GoFundMe page.
It read: “It is with great sadness, we have to let you know that our dear friend Nikki passed away in the early hours of Friday 9th April.
“It breaks our hearts to know that someone who is so precious was taken from us at such a young age. Nikki not only touched the lives of millions of people, but also her friends and family who will miss her immensely.
“We would like to request privacy at this difficult time, while Nikki’s friends and family process the sad news.
“Full details will be released as and when we know them.
“All donations have been greatly appreciated and it was heartwarming for everyone including Nikki to see how much she was loved.”
A statement from her representative said: “It is with immeasurable sadness that Nikki Grahame passed away in the early hours of Friday 9th April 2021.
“Please respect the privacy of Nikki’s friends and family at this tragic and difficult time.”
Her mother Sue Grahame told This Morning last week that Nikki’s condition deteriorated after the gyms closed.
Previously, Grahame said lockdown had been “hellish” and had “floored” her daughter.
Mrs Grahame told the Telegraph: “This last year has just about floored her… From the first lockdown, it was hellish. She struggled because she couldn’t go to the gym.
“Then in December she fell down and cracked her pelvis in two places and broke her wrist. I stayed with her for three or four weeks because she couldn’t do anything.”
Mrs Grahame continued: “We’ve been on this road a long time, 30 years on and off, and I’ve never seen her this bad. I’m frightened that I’ll die and she’ll have no one to support her. I don’t want her to go through any of this alone.”
She has written two books Dying To Be Thin in 2009 and Fragile in 2012 about her experiences.
Prior to finding fame on Big Brother, Grahame, then an aspiring actress, appeared as an extra in the BBC soap opera EastEnders and played a footballer’s wife in Sky One’s Dream Team.
She also appeared as a contestant on ITV dating show Blind Date and competed in the 2004 Miss Hertfordshire pageant.
After entering the Big Brother house dressed as a Playboy bunny, Grahame became known for her temper tantrums and Diary Room histrionics, including an infamous “who is she?” rant.
She formed a relationship with the show’s eventual winner Pete Bennett, but their romance ended a month after they left the house.
Grahame was evicted on day 58, but went back into the house after the remaining contestants picked her to return. She eventually finished in fifth place.
After Big Brother, she bagged her own reality show, Princess Nikki, which saw her try out various jobs.
She also appeared on Celebrity Scissorhands, 8 Out Of 10 Cats and The Weakest Link, and a Channel 4 poll named her the 12th most “written about” person of 2006 in the UK.
Today tributes were paid to the star.
Davina McCall, who hosted the reality series when it aired on Channel 4, tweeted she was “so desperately sad to hear” the news.
She added: “My thoughts are with her friends and family xx she really was the funniest , most bubbly sweetest girl x”.
Stars from the world of television who had met Grahame or worked with her also remembered her, with Coronation Street’s Daniel Brocklebank tweeting: “I’m deeply saddened to hear that Nikki Grahame has passed. We hung out a few times. The last time on stage together at Manchester Pride. A sweet, kind & fun lady. My love & thoughts go out to all who knew & loved her.”
Presenter Rylan Clarke-Neal said: “Thinking of Susan and Nikki’s close friends and family. A Big Brother Icon.”
Top Gear host Paddy McGuinness also remembered her, tweeting she was “definitely one of the stars from the glory years of reality tv. I met her a long time ago and she was a lovely girl. RIP young lady.”
Former X Factor star Joe McElderry said he was “grateful to have spent many fun times together” with Grahame, adding in a tweet: “My thoughts are with her family. Rest in Peace lovely girl.”
Reality star Mario Falcone wrote: “RIP Nikki Grahame. Sad news. Just 38 years old.”
Political commentator Owen Jones wrote: “Really upsetting to hear about Nikki Grahame. Anorexia is such a cruel illness. RIP.”
Writer Harrison Brocklehurst said: “ Absolutely devastated to hear the news about Nikki Grahame’s death. For people my age in 2006, she defined what it meant to be a reality tv personality before reality tv really became what it is now. Endlessly quotable, instantly beloved and a character no one will ever forget.”
Campaigner Juno Dawson added: “Nikki Grahame was a reality TV icon and I so dearly wanted her to be well. This is very sad.”