In every game that large health appears in, Large Health is a cube-shaped box with a red cross on it and it gives 50 health points when picked up. In Serious Sam 3: BFE, it is a small box with a cross on it.
Large Health usually appears before the player gets into a large battle or between waves of enemies in a large battle. While very useful, it should be reserved for until the player has around 60 or less health, or else its large amount of health points will be wasted.
It is also found in secrets, with some secrets containing just a Large Health.