Preliminary results indicate 99 per cent of people voted "yes" to independence, while in a presidential poll 96 per cent supported Eduard Kokoity, the current South Ossetian leader, Bela Pliyeva, the head of the election commission, said.
South Ossetia's leadership has described the referendum as a first step towards international acceptance.
No country is expected to recognise the result of Sunday's vote, although Russia has given de facto backing to the South Ossetian leadership and urged Georgia to accept the outcome.
Konstantin Zatulin, a member of Russia's parliament who was in Tshkhinvali to observe the referendum, said:
"We need to move towards recognising reality."
"South Ossetia is a reality, like Transdnestr, Abkhazia and Nagorny Karabakh," he added, referring to other disputed former Soviet regions.
Tbilisi, the Georgian capital, has repeatedly rejected South Ossetia's calls for independence and accused Moscow of trying to annex both South Ossetia and Abkhazia, another breakaway region.
Only 55,000 people were elligible
to vote in the referendum
No independent international monitors observed the polling, which has been widely criticised.
Jaap de Hoop Scheffer, the secretary-general of the Nato military alliance, said "such actions serve no purpose other than to exacerbate tensions in the South Caucasus region".
'Unhelpful and unfair'
The head of the 46-nation Council of Europe called the referendum "unnecessary, unhelpful and unfair".
"The results will not be recognised by the international community, the vote did nothing to bring forward the search for a peaceful political solution," Terry Davis, the secretary general of the human rights organisation, said.
The Organisation for Security and Cooperation in Europe (OSCE) called it "counterproductive".
Election officials said more than 90 per cent of the 55,000 eligible voters turned out for the the second vote on the province's independence since 1992.
South Ossetia declared independence after a war with Georgian forces in 1991-1992 that killed more than 1,000 people and displaced tens of thousands.