A Russian town, isolated for years from the surrounding influences of technology, finds itself subject to a terrible plague. The player controls one of three potential saviors, a government agent sent to the village (The Bachelor), an undertaker's son who has come to take over the business from his father (The Haruspex), and a young woman with mystical healing powers (The Devotress); the latter can only be played after having completed the game using one of the other characters. The three scenarios feature completely different missions, though their storylines are connected to each other.
Pathologic is a hybrid game that incorporates elements of role-playing and first-person shooter genres. The game world is viewed from a first-person perspective at all times. Much of the gameplay is dedicated to the exploration of the large town and conversations with its eccentric inhabitants, who will give the protagonist missions. Taking a cue from RPG quest design, some of these missions are entirely optional, while others serve the main storyline and trigger other quests.
The RPG angle is further emphasized by various statistics the player should pay attention to. The protagonists get hungry and tired, so acquiring food and resting from time to time is essential. The protagonists can also become infected by the mysterious disease, which is demonstrated by a corresponding status bar; medications of various kinds must be applied to lessen or cure the infection. The game has a precise internal clock, and its characters might change their locations regardless of the player's input, which makes some of the quests time-based. Completing the main quests, however, is only one of the requirements for reaching the best ending; the game's time will advance and events will occur even if the player character sleeps through the whole game (provided he/she has enough food for that time). The town must be saved in 12 days (game time); failure to do so will trigger one of the "bad" endings". The player is able to make moral decisions concerning saving characters or following one of the several leading groups in the game.
Combat in the game is action-based, following the FPS format. However, to emphasize the survival angle, all the three protagonists are rather clumsy and not particularly efficient in combat, and ammunition is scarce. Knives and other melee weapons can be used, as well as various guns. Weapons and clothes will become damaged and deteriorate; however, certain types of characters in the game will be able to fix them. Obligatory combat is rare in the game, though the player can kill any of the town's inhabitants, break into their houses, or fight criminals at night.
Economy and trading systems occupy an important portion of the gameplay. Prices in the shops will rise or fall depending on the current situation in the town. It is possible to sell any items the player finds in the game; however, another option is to trade them with the characters that roam the town. Depending on the character type, various trade possibilities are available, such as for example trading beads or needles that can be sometimes found in trash bins for valuable ammunition.