The identities of the shooter and the victims were not immediately available.
A gunman at a Chicago hospital killed a police officer and two others before dying in the shooting, while to the west of the country in Denver one person was shot and killed on a street corner and three others were wounded.
After shooting O'Neal, Lopez then killed a resident pharmacist, Dayna Less, and officer Samuel Jimenez during a shootout with police inside the hospital.
The shooter knew the doctor he shot outside Mercy Hospital, Chicago Police Superintendent Eddie Johnson said at a news conference, describing that initial killing as an act of domestic violence. She had nothing to do with nothing, and he shot her. Why?' Both of the women were taken to other hospitals nearby.
Mercy has a rich history as the city's first chartered hospital. Nearby buildings, including the National Teachers Academy, were locked during the attack.More news: At least three people dead after shooting and fire at huge mansion
Mercy Hospital later tweeted that all of its patients were safe. She is thought to have been known to him. "We heard more gunshots and arguing", a staff said. Records show that she sought the order but not whether she ultimately received one, Guglielmi said.
Her family said she had overcome a rare medical condition that caused her debilitating headaches throughout high school.
Thanksgiving week got off to a violent start Monday with four fatal shootings across the United States in a matter of hours.
Lopez had a permit to possess a concealed firearm, and it was unclear if officials knew about the 2014 complaint when the permit was granted, said Guglielmi, who said Lopez had legally purchased four guns in the last five years.
"Those officers that responded today saved a lot of lives", said Johnson.More news: Two in custody after little girl's body found on beach
Dayna Less, 25, was shot and killed during Monday's tragic shooting as she exited an elevator at Mercy Hospital, according to the Chicago Tribune.
O'Neal reported for work just before 3:30 p.m. when she was confronted by Lopez.
Police say the pharmacy assistant also killed in the shooting was unlucky enough to be getting out of a lift when she was hit by a stray bullet from the gunman.
In Philadelphia, two men and two women were "executed" in a home, according to ABC.
"Then nearly immediately, an officer was already coming in an SUV and he exchanged fire at them and then reloaded and shot the person on the ground again and then he made his way into the hospital and more shots were fired", another witness recalled.More news: Charles Howell III ends long wait for PGA Tour win