"Leinster Rugby can confirm that two members of the touring squad to South Africa, Isa Nacewa and Jamison Gibson-Park, encountered visa issues this morning upon arrival in Johannesburg," read a club statement.
"As this process is still ongoing, Leinster Rugby will be making no further statement."
Leinster have won both of their opening league matches so far this season with a try bonus point.
The news is a blow for the PRO14 ahead of the league's first-ever fixture on South African soil on Friday evening at the Nelson Mandela Bay Stadium in Port Elizabeth.
Leinster have travelled with a squad of 28 to South Africa but are without a number of senior players, largely due to injury.
Among hose ruled out through injury include Dan Leavy (ankle), Rob Kearney (hamstring), Jamie Heaslip (lower back), Richardt Strauss (knee) and Garry Ringrose (shoulder).
Second-rows Devin Toner and Scott Fardy were not considered for selection with their wives due to give birth in the next few weeks.