The Let Youth Lead advocates, who are chosen and supported by Harry's Sentebale charity, will welcome their royal guest, who is making a 10-day visit to Africa, to the northern city of Kasane.
Sentebale was co-founded by the duke in Lesotho in 2006 to help young people who have HIV, and three years ago its work expanded into nearby Botswana.
The country has the third highest HIV prevalence in the world and the duke's charity runs 47 Botswanan clubs supporting 1,300 HIV positive young people each month, through self-confidence building initiatives, practical health advice and peer-to-peer support.
Residential camps are also staged with the same aims and the numbers seeking help are growing.
Sentebale's Let Youth Lead advocates have lobbied on international platforms and met national figures since the initiative was set up to give young people a voice to debate issues that affect them, such as HIV/AIDS.
The young leaders will re-create a camp activity for Harry in which children are praised to boost their confidence using singing and dancing.
Harry will then join them for a discussion about why they represent their peers, before listening to a live broadcast of Sentebale's Radio Positive show hosted by two advocates on a popular FM station.
During his day in Botswana, Harry will join more than 200 schoolchildren and 30 teachers from 10 primary schools and two secondary schools for a tree-planting event in the Chobe Forest Reserve.
He will also board a Botswana Defence Force patrol boat to learn about the challenges the unit faces as they conduct river patrols to deter would-be poachers.