To determine who I think is going to win I am going to divide this into categories
Tactics: This category goes to Holmes, he is very smart compared to Jeffs average intellect. Therefore he will think out a better tactic and strategy to beat Jeff with no problem.
Experience: Again this goes to Holmes, he knows all sorts of different fighting styles he can use against him. Jeff is nothing new to Holmes, especially when Holmes actually mastered the ability to use weapons while Jeff really never showed any exceptional skill in wielding a knife.
Equipment: This edge also goes to holmes, his cane sword is covered in a deadly poison which is much better than a bloody knife Jeff found in his house to cut his smile with. Holmes also can also professionally use his pistols to full effect on Jeff considering he does not have protection against bullets. This means Jeff would likely have to tank the bullets, and to Jeffs credit, he would likely survive being shot with a gun considering the fact he has taken so much abuse from Slender himself. But Jeff brings nothing new to the table here.
Resistances: This category goes to Jeff, he is immune to sleep so fortunately for Jeff the pressure points are not going to affect him and since there is no prep time Holmes would not know this fact and this will result in Jeff taking advantage of this. And with his resistance to pain he can negate some serious injuries he may receive and this will allow him to persist in the fight. Holmes poison resistance is not going to come in handy here, (Unless Jeff somehow disarms Holmes and uses his weapon against him).
Weaknesses: Jeff will have a good advantage here since Holmes heavily relies on drugs.
Strength: This goes to Holmes, in a fist fight he would overpower Jeff and likely break Jeffs' bones and cause some heavy damage. The only thing Jeff has going for him here is that he won't feel it, allowing him to persist. But even then he can also grapple Jeff and overpower him allowing him to basically use one hand to shatter his skull. Also, one thing to note Jeff was able to hurt Slender with only a knife, there was no mention of him using his fist to deal heavy damage to Slender, and with Jeffs lack of knowledge of fighting skill, he would not even know how to throw proper punch. On the other hand Holmes knows how to fight allowing him to use his body at its full effect.
Durabillity: These 2 are tied here, If Jeff can survive being impaled by Slender I do not doubt Jeff can survive more than that, and Holmes has tanked alot of serious stuff too.
Overall: After analyzing these two a bit, Holmes is getting my vote.