Residents of the Abingdon area are being warned of a severe flooding threat between 7pm tonight and 9am on Tuesday.
Many houses are already flooded after the River Ock burst its banks.
Environment Agency spokesman Martin Townsend said: "We're going to see a second peak from the Thames tonight - it is a double threat."
He said the agency was mapping the floods but the scale of the threat had not yet been calculated.
Ian Travers Smith, an emergency planning officer for Oxfordshire County Council, said he was expecting many residents in the Abingdon and Oxford areas to be forced to spend the next two nights in emergency shelters.
"The scale of this is beyond that which we planned for," he said.
He advised those whose properties were at risk either to remain where they are and stay upstairs or to leave their homes and stay with friends and family.
"From my point of view the more people who help themselves, the better," he added.
In already-flooded streets, preparations were being made for the predicted onslaught.
Householders were barricading their doors with planks of wood and sandbags.
A list of streets in Abingdon likely to be affected by flooding was issued this evening.
People in the town are being given advice in the event that they may have to leave their homes this evening.
People who need to leave their homes are being advised to stay with friends or family elsewhere.
Those who need to be housed overnight should go to either Our Lady's Convent on the corner of Oxford Road and Radley Road, for the north area of the flooding, or Thameside School on the corner of Preston Road and Cotman Close for the south side of the flooded area. You will then be taken by emergency services to overnight accommodation.
Leaflets are being put through the doors of houses in all the roads that may be affected to explain the situation and give advice.
More information about flooding and what to do can be found on www.environment-agency.gov.uk or by calling Floodline on 0845 988 1188 The roads that are likely to be affected are:
AUDLETT DRIVE
BAILIE CLOSE
BURTON CLOSE
CALDECOTT ROAD
CHAUNTERELL WAY
COLERIDGE DRIVE
CULHAM ROAD
DRAYTON ROAD
EAST ST. HELEN STREET
FRANCIS LITTLE DRIVE
GODFREY CLOSE
HEALEY CLOSE
HERMITAGE ROAD
JENYNS COURT
MANOR COURT
MARCHAM ROAD
MEADOWSIDE
MEDLICOTT DRIVE
MILL PADDOCK
MILL ROAD
MILL STREAM COURT
MUSSON CLOSE
NASH DRIVE
OCK MILL CLOSE
OCK STREET
ORPWOOD WAY
RILEY CLOSE
SHEPHERD GARDENS
SOUTH QUAY
ST. AMAND DRIVE
ST. HELENS WHARF
SUFFOLK WAY
SYMPSON CLOSE
TENNYSON DRIVE
THE BRIDGE
THURSTON CLOSE
TOWER CLOSE
TURBERVILLE CLOSE
WILSHAM ROAD
WORDSWORTH ROAD
WYNDYKE FURLONG.
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