But the umpires deemed that would not be possible when they called the game off shortly after 4:00pm local time (1500 GMT) as a series that had started during a nationwide heatwave ended in more familiar English conditions.
The abandonment meant left-hander De Kock was just eight runs shy of what would have been his 18th ODI century.
England had gone into the game looking to avoid a third consecutive white-ball series defeat under new captain Jos Buttler, who succeeded now retired 50-over World Cup-winning skipper Eoin Morgan, following T20 and ODI reverses against India.
South Africa won the toss, with both sides unchanged after England’s thumping 118-run win in a rain-affected match at Old Trafford which followed the Proteas’ 62-run triumph at Chester-le-Street.
England made an early breakthrough when Janneman Malan (11) hit left-arm quick David Willey straight to Jason Roy at point to leave the Proteas 24-1.
But De Kock was in fine touch as he completed his first fifty of the series off just 39 balls, with the 29-year-old reaching the landmark by hitting boundaries off successive deliveries from leg-spinner Adil Rashid.
South Africa accelerated following the loss of Malan and were 89-1 by the time wicketkeeper De Kock reached his half-century.
Rassie van der Dussen, who made a career-best 134 in the series opener, shared a second-wicket stand of 75 with De Kock before he holed out for 26 when sweeping against Rashid.
Rain first stopped play when South Africa were 119-2 in the 21st over.
De Kock deployed the reverse sweep to good effect when play resumed in a match now reduced to 45 overs per side before a fresh downpour ended the match.
England and South Africa are scheduled to begin a three-game Twenty20 series at Bristol on Wednesday.