Dillon Croud is only two and was diagnosed with cancer in June, while eight-year-old Harry Brown is battling leukaemia.
Both will don their Southend United football kit and walk out with the players for Saturday's derby match against Colchester United.
Dillon's grandmother Susan Croud, of Buckingham Road, Hockley, organised for him to be a mascot as a break from his treatment.
Mrs Croud said: "Dillon's football mad. He's not yet three, but has already undergone an amazing amount of treatment at Great Ormond Street Hospital. For a child of his age it's horrendous, but he's doing well and still has a sparkle in his eyes. I thought he deserved a treat. He would go to bed in his kit if he could."
Dillon had to have chemotherapy and one of his kidneys removed when a large tumour was discovered.
He has had four weeks of radiotherapy and now faces more chemotherapy, but the tumour hasn't returned.
His mum Sarah Croud, of Park Terrace, Westcliff, said: "It's been a whirlwind few months. Just before he had his operation I gave birth to my daughter Florence who arrived early. It was a stressful time. Each time we go back for scans before the chemo we keep our fingers crossed the tumour hasn't come back. It's been a lot to cope with, but Dillon has been amazing. He constantly surprises us. He's a normal almost three year old who is boisterous and loves football."
Dillon has written a letter in the programme for the game which says: "Football is my favourite, but unfortunately I have an illness which means I have to have regular treatment at Great Ormond Street and this leaves me very poorly. Playing football with my cousins is always fun and I'm very excited about being mascot."
Fellow football fanatic Harry, a pupil at Richmond Avenue Primary School, Shoebury, will join Dillon on the pitch.
He was diagnosed with leukaemia in August last year.
His treatment was arranged thanks to the Echo and Little Havens children's hospice where he goes for respite breaks.
His mum Sarah, 37, of Kenilworth Gardens, Westcliff, said: "He copes with it all better than I do. He's always smiling and cheeky. He is having ongoing chemotherapy and so hasn't been to school for 14 months. For the first six months of treatment he was wheelchair bound as it was so intense and affected his joints and he couldn't walk. For him to be able to do this is brilliant. I'll have trouble getting him off of the pitch."