Health officials are particularly concerned over vulnerable groups with pre-existing illnesses and those aged over 65.
The warning is effective from tomorrow evening, January 17 until the morning of Saturday, January 21.
The cold weather is expected to lead to a rise in deaths as the whole region is affected.
The alert, which is also in place for regions including the North West, Yorkshire and The Humber, and the Midlands, warns of significant risks to health and pressures on social care services as temperatures drop.
The North East has been assigned a risk score of 7 under the Cold-Health Alert System, indicating a medium likelihood of minor impacts.
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However, neighbouring Yorkshire and The Humber face a higher risk score of 9, signalling the potential for more significant effects on health and a further demand on healthcare services.
The UK Health and Safety Agency have issued guidance to those who are particularly vulnerable during these bad weather spells by keeping rooms at a minimum of 18C and to make sure that they look our for those who may be affected by the weather.