The Proteas Women were 55-3 at stumps on a rain-affected day three of the one-off Test in Taunton, still 78 runs behind England.
Having been 328-6 overnight, the hosts declared their first innings closed on 417-8 with Nat Sciver unbeaten on 169.
Kate Cross then had opener Andrie Steyn caught for three as the Proteas went into a lengthy rain break on 9-1.
When play resumed, Laura Wolvaardt and Lara Goodall steadied the innings, before rain again forced the players off, 12.1 overs into the innings.
They were able to return, however, for another 12.5 overs, in which Issy Wong picked up two more wickets for England – those of Goodall (26) and Wolvaardt (16).
Proteas captain Sune Luus (4*) and Tumi Sekhukhune (1*) will be at the crease when the final day’s play begins on Thursday.