To obtain, something of equal value must be lost.
In Sekiro: Shadows Die Twice, Dragonrot is the cost Wolf must pay for his immortality, and unfortunately for everyone else, he never has to pick up the tab. Only the people Wolf meets suffer the effects of the disease. You'll know the plague is beginning when, after resurrecting one too many times, Wolf awakens in the Dilapidated Temple beside the coughing Sculptor. You'll be given a warning, in the form of Rot Essence, that he's caught Dragonrot. If you continue to abuse Sekiro's resurrect mechanic, he won't be the last.
Understandably, it's a little scary the first time you're told about the disease. Sekiro makes no mention of Dragonrot--or any downside to resurrecting--before this moment, and the game does little to immediately explain exactly what it is or how you can cure it. If you're looking to understand Rot Essence and Dragonrot, you've come to the right place. Below, we discuss exactly what both are, as well as how to cure Dragonrot and why you want to.
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Dragonrot has the potential to infect almost every character Wolf meets and interacts with on his journey. Although you don't get a cutscene for anyone but The Sculptor, the game will give you another Rot Essence whenever someone else has caught the plague. You can go and try and talk to them if you want, but the only response you'll get from many of them are violent coughing fits.
Bing able to talk to people is why you need to cure Dragonrot. Thankfully, as far as we can tell, no matter how many times Wolf resurrects in battle, no one will actually die from disease. So you don't have to worry about that. However, you cannot complete side quests for characters who are infected with Dragonrot, so if you want to experience everything Sekiro has to offer and unlock some of the game's best prosthetics, you'll need to keep people healthy.
Even if you don't care about finding everything, fixing Dragonrot assures you can take advantage of one of Sekiro's best features. Upon death, Wolf has the potential of receiving Unseen Aid, which prevents him from losing experience and sen. You need to former to unlock new abilities and the latter to buy items. Your chances of receiving Unseen Aid diminishes with every person who catches the Dragonrot. Refusing to cure the Dragonrot means, eventually, every one of Wolf's deaths will result in loss.
Unfortunately, you can't be proactive with finding a cure. You'll need The Sculptor to fall ill to the Dragonrot to open the questline you need. As soon as the game tells you The Sculptor is sick, talk to Emma. She'll tell you about a possible Dragonrot cure, but she'll need two samples of infected blood in order to create the medicine. So you'll need to resurrect a few more times to spread Dragonrot to another person. Shouldn't be too hard to die and resurrect a few more times considering how difficult Sekiro is.
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When you get the warning about a second infected person, go find them and let them cough their infected blood onto you. Return this to Emma and she'll craft the cure, a Dragon Tear. Using a Dragon Tear at an idol immediately cures all infected individuals of the Dragonrot. But it's only temporary. Resurrecting too many times again will once more cause the Dragonrot to spread amongst the populace. You'll need to buy more Dragon Tears from specific merchants if you want to cure the Dragonrot again--each goes for 180 sen. In our time with the game, we haven't discovered a merchant who sells an infinite number of Dragon Tears, though. So save those Dragon Tears for when you really need them, and just try not to resurrect too many times to prevent the Dragonrot from spreading. There doesn't seem to be a permanent cure for Dragonrot (other than just never resurrecting), so be careful.
In our Sekiro: Shadows Die Twice review-in-progress, Tamoor Hussain gave the game a 9/10, writing, "Sekiro marries From Software's unique brand of gameplay with stealth action to deliver an experience that is as challenging as it is gratifying."