What does Psalm 38:21 mean?

As part of his humble, trusting repentance for sin (Psalm 38:1–4, 8, 18), David pleads with God to stay with him and guide him through this experience. He trusted in the Lord as his personal God. David's cry here is not one of despair, but of faithful confidence (Psalm 38:22). What he prays here reflects an intense experience, not a sudden loss of confidence in the Lord.

On the cross, Jesus, David's chief descendant, experienced the pain of separation from God. He took on our sin (2 Corinthians 5:21), and God is righteous and holy. Christ's experience on the cross represented a difficult-to-define experience of separation, in some form, between God the Father and God the Son. This is likely one reason Jesus cited Psalm 22, calling out, "My God, my God, why have you forsaken me?" (Matthew 27:46). Jesus willingly endured that experience so He would never have to abandon those who trust in Him as Savior. Hebrews 13:5–6 exhorts: "Keep your life free from love of money, and be content with what you have, for he has said, 'I will never leave you nor forsake you.' So we can confidently say, 'The Lord is my helper; I will not fear; what can man do to me?'"