The South Africa Test skipper, who missed the preceding T20I series to be with his wife for the birth of their first child, will not be able to join the squad in time for the first Test after opting to extend his stay owing to a "difficult delivery."
Dean Elgar, 30, will thus become the 12th player to captain South Africa since their readmission, as the second-ranked Test nation look to reprise their successful trip to the UK from five seasons ago, when the Graeme Smith-led side won the three-match series 2-0.
"Faf's wife gave birth to their first child last week but the difficult nature of the delivery has delayed his return to the UK," Team manager, Dr Mohammed Moosajee said. "The mother and baby have settled at home, but he will be unable to make it back in time to take part in the first Test match. He will link up with the squad in the UK later this week."
In du Plessis's absence, South Africa are likely to field a rejigged and relatively inexperienced batting line-up at Lord's. Theunis de Bruyn, who opened on debut versus New Zealand at Hamilton and scored 0 and 12, could move down the order with Heino Kuhn potentially slotting alongside the stand-in captain at the top.
Aiden Markram, the other youngster in the squad, didn't play the warm-up clash at New Road but could still edge out de Bruyn after the latter bagged a duck in that fixture against England Lions.
The first Test begins on July 6 with subsequent games scheduled at Trent Bridge (July 14), The Oval (July 27) and Old Trafford (Aug 4).
South Africa's Test squad:
Faf du Plessis (c), Hashim Amla, Temba Bavuma, Theunis de Bruyn, Quinton de Kock (wk), JP Duminy , Dean Elgar (stand-in captain), Heino Kuhn, Keshav Maharaj, Aiden Markram, Morne Morkel, Chris Morris, Duanne Olivier, Andile Phehlukwayo, Vernon Philander, Kagiso Rabada.