Fifty people were killed and 53 more injured, making the terrorist act the deadliest mass shooting in US history.
"Shocked by the senseless tragedy in Orlando. We must stand together against hate and intolerance," DiCaprio wrote.
"What has happened in Orlando is Devastating. My heart Goes Out to all the Victims of the Shooting and to their Families. Stop Hate Crimes," Madonna posted in Instagram.
Pop star Gaga said, "I pray for all the victims families during this shooting epidemic. That their pain be met with compassion and support from the world."
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Oscar-winning actress Patricia Arquette, wrote, "Just heard about the horrifying attack in Florida. My love and prayers go out to our brothers and sisters. Heartbreaking."
DeGeneres tweeted simply "Sobbing" to her more than 60 million followers.
Caitlyn Jenner said, "Shocked & heartbroken. Sending all my thoughts & prayers to my bothers & sisters in Orlando. Be safe the rest of this weekend friends #pride."
"I just can't believe this is the world we live in today," Katy Perry tweeted.
Actor Neil Patrick Harris said, "The tragedy in Orlando is just beyond sad. My deepest regrets to all those suffering. There are no words that suffice. I'm...Stunned."
Justin Timberlake posted, "What gives? My heart is breaking right now for the victims and families of this heartless act. I just don't get it. #PrayForOrlando."
"My heart is breaking for you #Orlando! Sending love to all those affected by this ridiculous violence...," Enrique Iglesias said.
"Heartbroken for my LGBTQ brothers & sisters. Time for change. #GunControlNow," he wrote.