The fast bowler sustained a left hamstring injury during the Proteas' opening match against Namibia on Friday, managing only nine deliveries before leaving the field. He subsequently missed Saturday's victory over Zimbabwe.
Andile Simelane has been called up as Sipamla's replacement. The seam-bowling all-rounder has featured in 10 T20Is for South Africa.
Sipamla's absence adds to a growing list of fitness problems for the Proteas. Jason Smith was ruled out of the Namibia trip with a groin injury and was not replaced, while Kagiso Rabada is recovering from a right hamstring injury and has already been ruled out of the upcoming limited-overs series against Australia.
Rabada's availability for the Test series against Australia, which begins on October 9, will be assessed closer to the time.
Despite the latest setback, South Africa remain in contention in the tri-series after recovering from their surprise defeat by Namibia with a convincing win over Zimbabwe. Dewald Brevis was the standout performer, smashing an unbeaten 75 from 32 balls.
The Proteas have two more scheduled T20Is in the round-robin stage, with a potential third if they reach the final. They will then face Namibia in a three-match ODI series.
Their workload remains significant beyond the current tour, with Australia due to visit for white-ball and Test cricket before South Africa travel to Bangladesh for a full tour. England will then visit for a series featuring Tests and ODIs before the next SA20 campaign.
CSA also confirmed that Western Province seamer Tshepo Moreki has been added to the South Africa A squad for their one-day series against Bangladesh A.
Proteas middle-order batter David Bedingham continued his fine form ahead of a packed international home summer with yet another century for Durham in the English County Championship.
The Proteas could be without Kagiso Rabada for their entire three-Test series against Australia after the fast bowler suffered a serious hamstring injury.
Duan Jansen took three wickets while Dewald Brevis smashed an unbeaten 72 from 32 balls as the Proteas bounced back from an opening defeat to beat Zimbabwe by seven wickets in the T20 tri-series clash in Windhoek.
Namibia produced another upset against the Proteas, defending 163 to secure an 18-run victory in the opening match of the T20I tri-series in Windhoek on Friday.
