Austin Larry Mostrong, 20, and 19-year-old Preston Autry Mostrong allegedly attacked 50-year-old George Lowery in the area of Chubb Lane and North Magnolia Avenue in Santee on the night of April 24.
Lowery's wife, who lived with him in a nearby makeshift encampment, found him unconscious in the river bottom, suffering from severe trauma to his upper body. The victim also had been robbed, sheriff's Lt. Kenneth Nelson said.
Lowery was admitted to Sharp Memorial Hospital in grave condition and pronounced dead four days later, Nelson said.
Bail was set at $3 million for each of the brothers. They are due back in court May 16 for a preliminary hearing, and they face 25 years to life in prison if convicted.
Although prosecutors did not disclose any possible motive for the crime, sheriff's investigators said earlier they believe the fatal assault stemmed from a fight the older brother had gotten into with some homeless people in the same general area on April 20. It was unclear if Lowery had been present during that altercation, which left Austin Mostrong under arrest.
The suspects, who live in Santee, were booked into San Diego Central Jail on Thursday night.
Deputy District Attorney George Modlin said Preston Mostrong admitted hitting Lowery and throwing him into the weeds, tied up.