See main article: 2008 Copa Libertadores. The First Stage of the 2008 Copa Santander Libertadores began on January 29 and ended on February 12. Twelve teams qualified directly on this stage.
Team #1 played the second leg at home.[1]
| Teams | Scores | Tie-breakers | ||||||
|---|---|---|---|---|---|---|---|---|
| Team #1 | Team #2 | 1st leg | 2nd leg | |||||
Lanús  | 3:1 |  Olmedo | 0–1 | 3–0 | +2:−2 | — | — | |
| 3:6 |  Cruzeiro | 1–3 | 2–3 | — | — | — | ||
Mineros de Guayana  | 2:3 | Arsenal | 0–2 | 2–1 | −1:+1 | — | — | |
La Paz  | 1:2 |  Atlas | 0–2 | 1–0 | −1:+1 | — | — | |
| 0:1 |  Cienciano | 0–1 | 0–0 | — | — | — | ||
| Audax Italiano | 4:4 |  Boyacá Chicó | 3–4 | 1–0 | 0:0 | 3:0 | — | |
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Lanús and Olmedo tied 3–3 on points. Lanús advanced on goal difference.----Cruzeiro advanced 6–0 on points.----Mineros de Guayana and Arsenal tied 3–3 on points. Arsenal advanced on goal difference.----La Paz and Atlas tied 3–3 on points. Atlas advanced on goal difference.----Cienciano advanced 4–1 on points.----Boyacá Chicó and Audax Italiano tied 3–3 on points. Audax Italiano advanced on away goals.