Interior Ministry spokesman Maj. Gen. Mansour al-Turki said nine other people were wounded in the attack, three of them seriously.
A Saudi Interior Ministry official told the Associated Press that the bomb targeted police trainees as they were in the middle of prayer. The official, who spoke to AP on condition of anonymity because he was not authorized to speak to reporters, could not immediately confirm if the mosque was in an Interior Ministry compound.
State media reported that the mosque belongs to an Interior Ministry emergency services post in Abha, the capital of Asir province.
ISIL's local affiliate has claimed responsibility for a number of attacks in recent months, including various deadly shootings and smaller attacks against police at checkpoints in the capital, Riyadh.
Thursday's attack was the deadliest against Saudi security forces since ISIL attacks began in the kingdom last year.
In November a gunman opened fire at a mosque in the eastern Saudi village of al-Ahsa, killing eight. A suicide bomber that struck a Shia mosque in the eastern village of Qudeeh in May of this year killed 22 people. That was the deadliest such assault in Saudi Arabia in more than a decade. A week later a suicide bombing outside another eastern Shia mosque left four people dead.
Saudi authorities last month announced the arrest of more than 400 suspects in an anti-terrorism sweep. They said at the time that they thwarted other ISIL attacks being plotted in the oil-rich kingdom, including a suicide bomb plot targeting a large mosque in eastern Saudi Arabia that can hold 3,000 worshippers, and attempts to attack other mosques, diplomatic missions and security bodies.
Saudi Arabia is leading a coalition targeting Iran-allied Shia rebels in neighboring Yemen, not far from Abha. The rebels have carried out a number of cross-border attacks against military targets.
Al Jazeera and The Associated Press