Like Psalms 38 and 39 (and perhaps 40), David composed Psalm 41 when he was severely ill. And like Psalm 40, this song contains a prophetic foreshadowing of events in the life of the Messiah.

Before asking God to heal him in verse 4, David first lays a foundation for that request: "Blessed is he who considers the poor" (verse 1)—or "weak" (NIV). God will deliver, preserve, bless, protect, strengthen and—directly pertinent to David's situation—“sustain him on his sickbed and restore him from his bed of illness" (verse 3, NIV). David is a compassionate man. It is his practice to pray, fast and mourn for others when they are sick (Psalm 35:13-14). He trusts that God will intervene for him now in his own need (41:3).

Indeed, note that the final verse of the previous psalm reflected on God thinking on David himself in his poor and needy state (Psalm 40:17). Such concern for others in need is the heart of godly character, which God's people must emulate. David well understood this, being a "man after [God's] own heart" (Acts 13:22). The qualities of mercy and compassion figure prominently in the New Testament. The apostle James declares that showing concern for others is an essential element in true religion: "Pure and undefiled religion before God and the Father is this: to visit the orphans and widows in their trouble, and to keep oneself unspotted from the world" (James 1:27). Jesus taught, "Blessed are the merciful, for they will be shown mercy" (Matthew 5:7). He gave His disciples a sobering parable on the subject of compassion (Matthew 18:21-35) and stated that mercy (the word here denoting compassion or pity) is one of the weightier matters of God's law (Matthew 23:23).

Yet as important as it is for all to have concern for the weak—for the lowly and downtrodden—it is especially so of a king such as David, whose duty is to emulate God's righteous rule in defending the powerless (compare Psalm 72:2, 4, 12-14; Psalm 82:3-4; Proverbs 29:14; Psalm 31:8-9; Isaiah 11:4; Jeremiah 22:16). Again, David well knew this—and lived accordingly (as did and does Jesus Christ, who is prefigured in this psalm).

David then prays for mercy and healing, confessing his sin. When we consider parallels with Jesus in this psalm, we realize that He did not sin. Yet the great suffering and anguish that came upon Him at the end of His physical life was the result of bearing the penalty of sin—not His own but that of the rest of mankind (David's included).

David speaks of enemies relishing the thought of his imminent death (verses 5-8), which Christ also endured.

We then arrive at verse 9, which ties directly to the life of Jesus. David speaks of betrayal by a "familiar friend," a close companion, who dined with him. Some have suggested that the reference here and in Psalm 55:12-14 is to David's friend and counselor Ahithophel, who joined Absalom's rebellion against David. This seems a rather likely explanation—although the Bible does not mention David being severely ill at that time (though it would not be surprising for deep anguish and depression on that occasion to have made him physically sick). Since the companion is not named, and since the Bible does not record every detail of David's life, it's of course possible that this was a different friend on a different occasion—the illness, as previously mentioned, perhaps being the plague that struck after the numbering of Israel.

Whatever the case, the most significant meaning here is not actually David's personal situation at all—but the fact that this was a prophecy of what would happen in the life of Christ. The Nelson Study Bible notes on Psalm 41:9: "The outrage of betrayal by one so close is nearly unbearable (Matt. 26:14-16). The fulfillment of this verse in the experience of Jesus and Judas is remarkable. Not only did the two eat a meal together (Matt. 26:21-25; Mark 14:18-21; Luke 22:21), but Jesus also called Judas a 'friend' at the moment of betrayal (Matthew 26:50). Moreover Jesus quoted this verse, noting its fulfillment in Judas (John 13:18)."

In Psalm 41:10, "Raise me up" was again David's prayer for healing—to be brought up from his sickbed. Yet "in another sense [given the clear messianic context of this psalm], these words look forward to Jesus' resurrection (Psalm 16:10, 11; Psalm 118:17, 18)" (note on Psalm 41:10-12). David expresses his belief in eternal life when He says confidently of God's salvation: "You...set me before Your face forever" (verse 12).

The psalm closes in verse 13 with the doxology (word of praise) that was most likely appended to the end of the psalm sometime later in compiling Book I of the Psalter or in even later arrangement.