Al Hilal, four-time continental champion, has set a blistering pace at the top of the SPL and went unbeaten in their Champions League group, winning five of their six games to qualify in first place.
On Thursday it was handed a trip to Iran as the AFC draw took place in Kuala Lumpur, with them scheduled to play the first leg away from home in early February.
Meanwhile, Cristiano Ronaldo and Al Nassr will have to meet Al Fayha.
The UAE side Al Ain will play Nasaf from Uzbekistan.
The final tie in the West section pits Karim Benzema and Al Ittihad against another Uzbek side in Navbahor.
AFC Champions League - Round of 16
First legs, Feb 12-14; Second legs, Feb 19-21
West section:
FC Nasaf (UZB) v Al Ain FC (UAE)
Al Fayha SC (KSA) v Al Nassr (KSA)
Sepahan SC (IRN) v Al Hilal SFC (KSA)
Navbahor (UZB) v Al Ittihad (KSA)