Yuvraj suffered a tear in his left knee during a warm-up ahead of Sunday's Champions Trophy clash against Australia here and was rushed to Mumbai to see the board's medical consultant Anant Joshi.
Yuvraj will be examined again in two weeks to determine if he will be available for the subsequent three-Test series in South Africa, Board of Control for Cricket in India secretary Niranjan Shah said
"According to the doctor, there is a tear in the interior cruciate ligament with some amount of bruising of the bone in the left knee and there is also a swelling of the knee," said Shah on Tuesday.
"The doctor has recommended some exercises and Yuvraj has been advised to use crutches to take the load off the knee.
"At this stage Yuvraj will be unable to participate in the one-day series in South Africa."
Wicketkeeper-batsman Dinesh Karthick, who was put on stand-by on Monday, will take Yuvraj's place in the 16-man squad which leaves for South Africa on Nov 13.
Yuvraj, who turns 25 on Dec 12, has scored 4,286 runs in 159 one-dayers at an average of 34.84. He has also played 19 Tests with 830 runs at 33.20.
Seamer Ajit Agarkar, who broke his left thumb against the West Indies last week, will undergo a fitness test on Nov 10 in Mumbai, Shah added.
If Agarkar is declared unfit, he will be replaced by young fast bowler Vikram Rajvir Singh.
India begin the six-week tour with a practice match against South Africa 'A' in Benoni on Nov 16.
The five one-dayers will be played in Johannesburg (Nov 19), Durban (Nov 22), Cape Town (Nov 26), Port Elizabeth (Nov 29) and Centurion (Dec 3).
A Twenty20 international, India's first, will be held in Johannesburg on Dec 1 between the fourth and fifth one-dayer.
The three Tests will be played in Johannesburg (Dec 15-19), Durban (Dec 26-20) and Cape Town (Jan 2-6).
Squad: Rahul Dravid (capt), Virender Sehwag, Sachin Tendulkar, Wasim Jaffer, Mohammad Kaif, Dinesh Karthik, Suresh Raina, Dinesh Mongia, Mahendra Singh Dhoni, Irfan Pathan, Ajit Agarkar (Vikram Rajvir Singh on standby), Munaf Patel, Shanthakumaran Sreesanth, Harbhajan Singh, Anil Kumble and Zaheer Khan Coach: Greg Chappell