The 32-year-old suffered a blow on the head off a Pakistan's paceman Mohammad Irfan's bouncer during his epic 234 in the second Test in Dubai last month, a match which South Africa won to level the series 1-1.
He managed to play the first two ODIs in the five-match series but was withdrawn before the third match played in Abu Dhabi on Wednesday.
Team manager Mohammed Moosajee said Smith suffered post-concussion.
"Graeme was symptom free after the blow except for a mild headache and tests at the time allowed him to continue playing. However, seven days post-injury, during the second one-day in Dubai he started complaining of blurred vision which progressed to dizziness, unsteadiness on his feet and difficulty focusing," said Moosajee.
"The MRI Scan was clear, however it is in keeping with the assessment of Post-Concussion Syndrome, which is usually a clinical diagnosis. Post-Concussion Syndrome can be described as a collection of symptoms that some people develop after they have experienced a minor traumatic brain injury otherwise known as concussion.
"Graeme will leave the tour on Thursday, and has been advised a rest period of at least two weeks by the medical team. He will continuously be monitored in the interim."
Smith was replaced by left-handed opener Quinton de Kock in the third match while Henry Davids will fly in as replacement for the remainder of the one-days.
Smith has so far played 112 Tests and 195 one-day matches for South Africa.
Graeme Smith out of Pakistan series with head injury
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