The animal rights campaigners, with the Brighton sector international grassroots organization DxE, entered the eatery wearing masks and carrying signs saying 'it's not food, it's violence'.
They then sprayed the floor and windows with fake blood.
'Born to be murdered'
One of the activists gave a speech, saying: "Born to be murdered, their flesh sold for profit. These are babies who feel fear and pain and seek comfort, like we all do.
"A cruel, violent and greedy system must be challenged. Who are we if we allow innocents to die? If we value, money, taste and convenience over life itself. The power we have over our fellow animals is not an invitation to exploit. Might is not right!"
Another added: "Because animals often can't fight back we feel like we can do as we please to them. Chickens crammed in cages, thrown on trucks. Babies torn from their mothers for their milk. Pigs unable to move in metal crates on cold, urine-soaked concrete floors. Fish farmed one on top another with no space but plenty of disease.
"Fish who did swim free pulled with a hook from the sea. Lambs taken screaming from their brothers and sisters before their throats are slit. Every single one sentenced to death so places like this can exist, so monetary value can be ascribed to their vulnerable little bodies."
"We can confirm an incident took place in our London Road restaurant [on Friday]," said a statement from McDonald's.
"Due to the mess and damage caused, the restaurant was closed from 7:30pm while the team worked hard to return the restaurant to normal, and we reopened at 5am today. We are supporting the police with their ongoing investigation and apologize to any customers adversely impacted by this incident."
The scene was attended by Sussex Police, who arrested one woman, who reportedly refused to leave the restaurant.