Religion, including Christianity, too often "breeds contempt" for gays, according to a senior Catholic bishop.
The Right Rev Robert Lynch, Catholic Bishop of St Petersburg, Florida, wrote on his blog: "Sadly it is religion, including our own, which targets, mostly verbally, and also often breeds contempt for gays, lesbians and transgender people."
Those killed by the gunman were all made in the image and likeness of God, he adds, and this is what the Church teaches.
"We should believe that. We must stand for that."
While deranged people do senseless things, everyone observes, judges and acts from some kind of religious background, Lynch said.
"Singling out people for victimisation because of their religion, their sexual orientation, their nationality must be offensive to God's ears. It has to stop also."
He also condemned those such as Republican presidential candidate Donald Trump who wish to ban Muslims from the US as "un-American".
"There are as many good, peace loving and God fearing Muslims to be found as Catholics or Methodists or Mormons or Seventh Day Adventists," he said.
Bishop Lynch also addressed the issue of gun control, arguing that in crafting the amendment on the right to bear arms, the founding fathers had no idea of the "weapons of mass destruction" their words would one day protect.
He said they would be "turning in their graves" and added: "It is long past time to ban the sale of all assault weapons whose use should be available only to the armed forces."
True pro-lifers should campaign for a ban on assault weapons like the guns used by the Orlando shooter, he continued.
"If one is truly pro-life, then embrace this issue also and work for the elimination of sales to those who would turn them on innocents."
Lynch's diocese is just to the west of Orlando where the shooting happened, and he has been in contact with Bishop of Orlando John Noonan.