The latest indictment charged the 22-year-old Tucson man with murder in the deaths of U.S. District Judge John Roll and Giffords aide Gabe Zimmerman. Loughner also faces new charges of causing death to or injuring participants at a federally provided activity.
Loughner had pleaded not guilty to earlier federal charges of trying to assassinate Giffords and kill two of her aides.
Federal prosecutors haven't yet said whether they will seek the death penalty against Loughner. But legal experts believe it's a virtual certainty.
In all, 13 people were wounded and another six people, including a 9-year-old girl, died in the attack.
Loughner also will likely face state charges in the attack, but will be tried first in federal court before any prosecution begins on state charges. Federal and county prosecutors said federal law requires state prosecutions to be suspended while a federal case is pending.
Loughner is scheduled for a court hearing on Wednesday in Tucson.
A day after the shooting, prosecutors filed a complaint in court charging Loughner with trying to assassinate Giffords, attempting to kill two of her aides and killing Roll and Zimmerman. Those charges were later replaced by federal indictments that mirrored the same charges.
In many criminal cases, prosecutors will often file charges themselves without a grand jury indictment, but will later replace those charges with an indictment. It's not known why the charges against Loughner weren't contained in one indictment.