The court, presided over by Judge Said al-Qata, confirmed the death sentence pronounced by a lower court on 29 September against Abd al-Rahim al-Nashiri, who is in US custody and was tried in absentia.
But it commuted the sentence against Jamal al-Badawi to 15 years.
The prosecution had asked for maximum penalties for the six men charged in July with the bombing, which killed 17 US sailors.
The men were accused of belonging to al-Qaida.
Al-Nashiri was arrested in the United Arab Emirates in October 2002 and handed over to Washington.
The prosecution had argued during the trial, which opened in June, that 38-year-old al-Nashiri was "the main bankroller of the attack."
Born in Saudi Arabia of Yemeni descent, al-Nashiri was described at the time as al-Qaida's chief for naval operations and its operations chief in the Gulf.
The USS Cole was attacked in
Yemen in 2000
He is also suspected of involvement in attacks against the US embassies in Kenya and Tanzania in August 1998 that killed 224 people, and in the October 2002 attack on the French super tanker Limburg off south Yemen in which one Bulgarian crew member was killed and 12 others were wounded.
But the prosecution's request for harsher sentences for the other Yemenis jailed in connection with the bombing was quashed.
The judge did not sentence to death Fahd al-Qasa, alias Abu Hadhifa, and Mamun Ahmad Said Amswa, both aged 30, who were originally jailed for 10 and eight years, respectively.
Instead of the prosecutor's call for capital punishment, Amswa had his sentence reduced to five years. Qasa's sentence was upheld.
The court also upheld the five-year sentences of Ali Muhammad al-Mirqab, 30, and Murad Saruri, 27, turning down the request from the prosecutor general that their prison terms be increased to eight years.
The US sailors were killed when two bombers on an inflatable raft blew themselves up alongside the USS Cole on 12 October, 2000 in Yemen's port of Aden.