The bomber, wearing a police uniform, made his way into a police compound in Tirin Kot, the capital of Uruzgan province, and blew up explosives attached to his body, Uruzgan police chief Juma Gul Hemat told Reuters.
"As a result of the suicide attack on a police unit [...] 21 police were martyred and eight more wounded," the Interior Ministry said in a statement.
Taliban insurgents claimed responsibility for the attack.
Separately, the Defense Ministry said Afghan troops arrested three would be suicide bombers Monday in another part of Uruzgan, which like most of the volatile south is an area of high Taliban activity.
The United States is considering requests from commanders for up to around 25,000 more US troops to be sent to Afghanistan, most of them to the south where mainly British, Canadian and Dutch troops are struggling to contain the Taliban insurgency.
Dutch and Australian troops are stationed in Uruzgan.
Some extra US troops have already begun arriving in Afghanistan, including 3,700 soldiers from a combat brigade, that deployed last month.