The State Department said the Southern African Development Community (SADC) was misguided in making the appeal and suggested its leaders did not understand the dire situation in Zimbabwe.
"The statements on Zimbabwean sanctions ... are disappointing and do not accurately reflect conditions on the ground," said Jo-Anne Prokopowicz, a department spokesperson.
She said Mugabe and his policies and not the sanctions were responsible for the poor economic and social conditions in which the people of Zimbabwe are now living and accused the government of manipulating the crisis to consolidate power.
"The humanitarian and economic crises in Zimbabwe are a direct result of failed Zimbabwean goverment policies," Prokopowicz said, citing the imposition of price controls, artificial exchange rates and a controversial land reform programme as examples.
She added that foreign and local investment in Zimbabwe had been paralysed by the Mugabe government's "decision to abandon the basic tenets of rule of law and democracy".
"There is clear evidence that the government is trying to consolidate its own political position with no regard for democratic institutions or the effect on the citizens of Zimbabwe," Prokopowicz said.
On Monday, Tanzanian President Benjamin Mkapa, the chairperson of the SADC, declared that US and European Union sanctions against Zimbabwe were unwarranted and ineffectual and called for them to be lifted.
The State Department ridiculed his allegation, noting that the sanctions affected only Mugabe and his inner circle and said that if southern African nations truly cared about the Zimbabwean people, they would work to isolate the government in Harare.
"SADC member states concerned about conditions in Zimbabwe should openly distance themselves from the failed economic and political policies of the Mugabe regime and press for full restoration of democracy and the rule of law," Prokopowicz said.
The US and EU sanctions were imposed last year over the effects of the Mugabe government's often violent land redistribution programme launched three years ago and his re-election in 2002 polls widely condemned as fraudulent.
The SADC includes Angola, Botswana, the Democratic Republic of Congo, Lesotho, Malawi, Mauritius, Mozambique, Namibia, the Seychelles, South Africa, Swaziland, Tanzania, Zambia and Zimbabwe. – Sapa-AFP.