The Hunter's top public health official says "Sydney should stay in Sydney" to give regions a "fair chance" to get vaccinated before the state starts opening up.
Parts of the Hunter have adult double-dose vaccination rates almost 20 percentage points behind the state average of 55 per cent.
The Hunter indigenous population is even more vulnerable with only 30 per cent double-dose coverage in people aged 15 and over.
NSW Health will hold a walk-in, no-booking vaccination clinic for the Aboriginal community on Saturday and Sunday from 9am to 3pm at the Belmont vaccination hub to help address the low coverage.
NSW could start opening up as soon as October 11, but Hunter New England Health public health controller Dr David Durrheim says any relaxing of restrictions should not include allowing Sydney people to travel to regional areas.
"There is a real charge towards opening up Sydney in three weeks and the regions are lagging behind in terms of vaccination rates," he told ABC Newcastle on Thursday.
"That is really worrying me.
"We need to grab every opportunity to get vaccinated but also to advocate that maybe at this stage Sydney should stay in Sydney and we'll rather move around within the regions, thank you very much."
Parliamentary Secretary for the Hunter Taylor Martin told the Newcastle Herald on Wednesday that the government was seeking feedback from regional mayors and MPs before deciding how to resume intrastate travel.
Dr Durrheim said his medical colleagues shared his "strong feeling" that regional NSW should have longer to increase vaccination rates.
He said only a "tiny minority" of Hunter and Central Coast residents were "anti-vaxxers" and those communities needed a "fair chance" to get vaccinated.
Federal government figures show 33 per cent of indigenous people in Newcastle and Lake Macquarie were fully vaccinated by September 21 and only 28 per cent in the rest of the Hunter.
Sixty-two per cent of the over-15 Hunter indigenous population had received one dose, well behind the state rate of 83.5 per cent.
Figures published early this week showed adult double-dose vaccination rates in the overall Muswellbrook population (34.1 per cent) were the lowest in the state.
Cessnock (36.9), Singleton (37.6) and Maitland (42.7) local government areas also lagged well behind the NSW average.
Upper Hunter LGA led the region with 51.2 per cent of those aged 16 over fully vaccinated, followed by Port Stephens (50.1), Lake Macquarie (49), Dungog (48.3) and Newcastle (47.4).