In weariness - Resulting from traveling, exposure, labor, and want. The word κόπος kopos (from κόπτω koptō, "to beat, to cut") means, properly, "wailing and grief," accompanied with beating the breast. Hence, the word means "toil, labor, wearisome effort."
And painfulness - This word (μόχθος mochthos) is a stronger term than the former. It implies painful effort; labor producing sorrow, and in the New Testament is uniformly connected with the word rendered "weariness" (1 Thess, 2-Corinthians 2:9; 2-Thessalonians 3:8), rendered in both those places "travail."
In watchings often - In loss of sleep, arising from abundant toils and from danger; see the note on 2-Corinthians 6:5.
In hunger and thirst - From traveling among strangers, and being dependent on them and on his own personal labors; see the note, 1-Corinthians 4:11.
In fastings often - Either voluntary or involuntary; see the note on 2-Corinthians 6:5.
In cold and nakedness - see the note, 1-Corinthians 4:11.

In weariness and painfulness - Tribulations of this kind were his constant companions. Lord Lyttleton and others have made useful reflections on this verse: "How hard was it for a man of a genteel and liberal education, as St. Paul was, to bear such rigours, and to wander about like a vagabond, hungry and almost naked, yet coming into the presence of persons of high life, and speaking in large and various assemblies on matters of the utmost importance!" Had not St. Paul been deeply convinced of the truth and absolute certainty of the Christian religion, he could not have continued to expose himself to such hardships.

In weariness and (r) painfulness, in watchings often, in hunger and thirst, in fastings often, in cold and nakedness.
(r) Painfulness is a troublesome sickness, as when a man who is weary and wants rest is forced to begin new labour.

In weariness and painfulness,.... Through long journeys and frequent preaching; or "in labour and trouble"; or in troublesome labour, for all labour is not so; as hunting, hawking, &c. though laborious, yet delightful; but the labours of the apostle were painful and troublesome to the flesh, though he had much inward spiritual delight and pleasure in them:
in watchings often; being sometimes engaged at midnight, either in preaching, or praying, or staging psalms, and sometimes obliged to work early and late with his own hands to supply his necessities:
in hunger and thirst; as when at sea, or in wilderness places, or where no notice was taken of him for preaching the Gospel; he doing that freely without asking the assistance of any, which in some places would have been prejudicial to his designs, and the spread of the Gospel:
in fastings often; voluntary ones, which he engaged in, not as meritorious works, but to keep under his body, and as proper to attend the work of prayer at certain times:
in cold and nakedness; when travelling in the winter season, and but poorly clothed to keep him from the inclemencies of the weather; and having no certain dwelling place to retire unto and abide in, during any severe season there might be, and wanting the comforts of life to support him under such inconveniences.

fastings--voluntary, in order to kindle devotions (Acts 13:2-3; Acts 14:23; 1-Corinthians 9:27); for they are distinguished from "hunger and thirst," which were involuntary [GROTIUS]. However, see on 2-Corinthians 6:5. The context refers solely to hardships, not to self-imposed devotional mortification. "Hunger and thirst" are not synonymous with "foodlessness" (as the Greek of "fasting" means), but are its consequences.
cold . . . nakedness--"cold" resulting from "nakedness," or insufficient clothing, as the Greek often means: as "hunger and thirst" result from "foodlessness." (Compare Acts 28:2; Romans 8:35). "When we remember that he who endured all this was a man constantly suffering from infirm health (2-Corinthians 4:7-12; 2-Corinthians 12:7-10; Galatians 4:13-14), such heroic self-devotion seems almost superhuman" [CONYBEARE and HOWSON].

In cold and nakedness - Having no place where to lay my head; no convenient raiment to cover me; yet appearing before noble - men, governors, kings; and not being ashamed.