A third patient, who had been discharged, also tested positive and died, although the virus was not the primary cause of death.
The Co Armagh hospital is battling outbreaks in its Emergency Department, Haemotology Ward and Ward 3 South.
Northern Ireland Health Minister Robin Swann described the deaths as “extremely distressing and disturbing”.
The Southern Trust announced on Friday that two patients connected to the Haematology Ward, who had tested positive with Covid-19, had died within the last 48 hours.
“We are profoundly sorry about these deaths and extend our deepest sympathies to the family and friends of those who have passed away,” the Trust said in a statement.
“A third patient who had been treated on the Haematology Ward was discharged home and has since sadly passed away with a Covid-19 positive diagnosis, but this was not the primary cause of death.”
The total number of patients connected to the Haematology Ward at Craigavon Area Hospital who have tested positive remains at 14.
Seventeen members of staff have tested positive and are currently off and self-isolating.
A total of 42 staff members have been identified as potential contacts and are currently self-isolating.
The ward remains closed to new admissions. The Trust said there are no further cases of the virus in the Emergency Department, which it described as operating as normal.
On Ward 3 South, two members of staff and one patient have tested positive, while 14 staff members are currently self-isolating.
In total, there are currently 56 staff who are connected with clusters at Craigavon Area Hospital who are off work and self-isolating.
“There are other staff across the Trust self-isolating, and these are a mix of clinical and non-clinical staff,” the Trust added.
“This will generally relate to family/social contacts where guidelines require a period of 14-day self-isolation.
“This has been ongoing since the start of the pandemic and we expect will continue throughout the winter.”
Mr Swann said: “My deepest sympathies go to the families and friends of those who have passed away.
“The Southern Trust has made clear that a detailed investigation is ongoing following the clusters at the hospital.
“This situation demands a thorough and expeditious investigation.
“Patients and bereaved families are entitled to answers.
“I will continue to closely monitor the management of these clusters and will be receiving updates from the Trust.”
