The duo had been expected to start for the Boks in the opening game of the Red Rose's tour but head coach Rassie Erasmus has now revealed that neither will feature in Johannesburg.
Both men were involved in Montpellier's Top 14 final loss to Castres last weekend and will only link up with the rest of the South Africa squad in midweek, leaving them with little time to prepare for Saturday's Test match.
"I won't consider them this week just because they haven't trained with us much, and it wouldn't be fair on the guys that have been with us here this whole time," said Erasmus.
"I also want to see what they look like when they get here."
The decision not to include either Du Plessis or Steyn in his squad for the first Test will likely force Erasmus to turn to members of the inexperienced party he took to the United States for last Saturday's clash with Wales.
The Boks narrowly lost to the Welsh in Washington and the head coach hopes experienced players coming back into the squad to face England will stand them in good stead if the first Test also proves to be a tight contest.
"There is no doubt that we saw that there is potential but we were perhaps lacking the experience, and the combinations were a bit disrupted," he added.
"Most of the guys who stayed behind have a bit more experience and we will need that against England."