Experts from the NHS, private and academic sectors will work together in Attercliffe to develop cutting-edge treatments for long-term conditions such as asthma and diabetes, as well as debilitating muscular and skeletal problems.
Sheffield Children's Hospital will be the lead in the new Centre for Child Health Technology, while Sheffield Teaching Hospitals will create the Orthopaedic and Rehabilitation Research and Innovation Centre.
Experts would work alongside colleagues at Sheffield Hallam University's Advanced Wellbeing Research Centre, which will focus on innovations that will 'improve the health of the nation'.
Olympic Legacy Park project lead Richard Caborn, a former sports minister, said: “These two centres are the latest evidence of Sheffield taking a world-leading role in tackling a range of health issues and encouraging people to live healthier and more fulfilled lives.
“Not only will they ensure a firm and lasting legacy from the 2012 London Olympics, but together they will make a significant contribution to the objectives outlined in a number of key Government and NHS health and business strategies.”
The two new centres are expected to create almost 3,500 jobs by 2027, including 348 professional roles.
Those behind the projects predict each Â£1 of public investment will generate around Â£14.50 towards the economy by 2042. The centres therefore have the potential to generate Â£1.7 billion in gross value added benefits to the economy by 2042.
Mr Caborn has been in talks about the centres with Lord Carter, a non-executive director of NHS Improvement who was a board member of the 2012 Olympic bid.
The OLP project lead has also written to the secretary of states for business, education, infrastructure and skills and health along with the chancellor, asking for the two projects to be included in the Government's industrial and life sciences industrial strategies.
Oasis Academy Don Valley and Sheffield UTC Olympic Legacy Park are already up and running on the former Don Valley Stadium site. Also planned is an indoor arena that will be the home of Sheffield Sharks basketball, along with community clubs, and a stadium to be shared by Sheffield Eagles rugby league team and Sheffield United Ladies.