Red Dead Redemption 2 is a huge game, so much so it might be tempting to beeline through the story and finishing up the side missions after. Unfortunately, this doesn't work for a number of reasons.
There are several missions throughout the game that you can't access after completing the story, or even if you progress in the story without completing them.
Those missions which other gang members give you are definitely among those that you should complete before progressing to the next chapter.
Other missions that become inaccessible after making too much progress are several Honor missions. These are tied to the "Lending A Hand" trophy that requires you to finish all Honor missions.
Currently, the trophy is slightly bugged - some players who complete all Honor missions don't get it, while others who don't complete all do get it. You can expect this to be patched soon, thus making it necessary to finish these missions.
The list of missions you should complete within the chapter that they are given are as follows:
- Money Lending and Other Sins I, II, III - To finish the mission, you need to turn in the debts.
- Good, Honest, Snake Oil - Go to the Sheriff's Office in Valentine to meet the quest giver.
- We Loved, Once and True I, II, III - This mission is triggered by the letter found in Arthur's tent.
- Pour Forth Oil II
- Home Robbery With Javier
- Debt Owed By Mr. Wrobel
- Debt Owed By Chick Matthews
- Debt Owed By Lilly Millet
- Hunting With Charles
- The Course of True Love I, II, III - This quest is given by Beau Gray in Rhodes.
- Money Lending and Other Sins IV
- Home Robbery With Sean
- Fishing With Kieran
- Fishing With Javier
- Debt Owed By Gwyn Hughes
- Debt Owed By Winston Holmes
- Help a Brother Out - Given by Brother Dawkins in Saint Denis.
- Brothers, Sisters, One and All - Also given by Brother Dawkins in Saint Denis.
- Fatherhood and Other Dreams I, II - This quest is triggered by a letter in Arthur's room.
- Money Lending and Other Sins V
- High and Low Finance (Exclusive for Special/Ultimate Edition) – It is marked as a Bank Robbery Companion activity
- Coach Robbery with Micah
- Coach Robbery with Lenny
- Debt Owed by Algie Davidson
- Hunting with Pearson
- Rustling with Uncle
- Savagery Unleashed
Please note that the whole chapter 5 is only accessible once it is available for you to play. After this chapter finishes you will not be able to return to this chapter for whatever exploration you want to do. If you want to explore and check the area out in Chapter 5, do so while you are still in this chapter,
This makes pretty much every mission in this chapter missable entirely, with an exception of The Wisdom of the Elders and The Veteran stranger missions, which can be played later.
- The Course of True Love IV, V - This quest is triggered by a letter from Penelope Braithwaite
- Archeology for Beginners - Given by Rains Fall at the Indian reservation.
- Honor, Amongst Thieves - Given by Captain Monroe at the Indian reservation.
- Money Lending and Other Sins VI, VII - Like in the first three sections, you need to turn in debts to complete the mission.
- Do Not Seek Absolution I, II - Given by Edith Downes in Annesburg. This is easy to miss since it is only accessible if you have an Honor level of 4.
- Mrs. Sadie Adler, Widow I, II
- Of Men and Angels I, II
- Debt Owed by J. John Weathers
- Debt Owed by Arthur Londonderry
If you complete these side missions as well as those which your fellow gang members give you, you should have your bases covered in terms of missable content.
A few Strangers missions are also inaccessible after you finish the main story, but can be played at any point before the epilogue. Besides, once you do reach the epilogue, you'll be busy exploring the newly unlocked section of the map.