Overnight into Wednesday, Michigan City Parks and Recreation said two animals died due to "separate medical events."
A wolf died from natural causes and a lemur died due to lung failure.
Officials said after the wolf died, there was an "incident" between other wolves and animal care staff.
A spokesperson for the department said "all involved are stable."
The zoo opened to the public on Wednesday. However, the main wolf exhibit will be closed while staff "assess the situation."
Police said two injured staff members, ages 39 and 34, were stabilized at the hospital with non-life-threatening injuries, but their current conditions were unknown. The 39-year-old worker had sustained serious injuries across their entire body.
"I'm surprised that would happen because it looks like multiple cages where they're separated," zoo visitor Erin Graham said. "The animals were mostly sleeping while we were in there, so I'm really surprised that a zookeeper got attacked."
No other information was available.