Angiogenesis is essential for breast cancer metastases formation and is mediated by vascular endothelial growth factor (VEGF) and prostaglandin E2 (PGE2). We hypothesized that serum levels of VEGF and PGE2 are increased by the stress response to breast cancer surgery and attenuated by paravertebral anesthesia and analgesia (PVAA). Thirty women undergoing mastectomy were enrolled in this prospective, randomized study, to receive general anesthesia (GA) and postoperative opioid analgesia (morphine 0.1 mg/kg bolus and patient-controlled infusion) or GA and PVAA (72-h infusion). All patients received rectal diclofenac. Venous blood samples were taken preoperatively and at 4 and 24 h postoperatively for serum glucose, cortisol, C-reactive protein, VEGF, and PGE2. PVAA inhibited the surgical stress response, as indicated by significantly less plasma glucose, cortisol, and C-reactive protein. VEGF and PGE2 values did not differ significantly between the groups. Mean (sd) percentage change in VEGF at 4 and 24 h respectively were 3% ± 44% versus 9% ± 80%, P = 0.29 and 5% ± 43% versus −10% ± 63%, P = 0.41 for patients with combined general and PVAA and GA alone, respectively. Mean percentage change in postoperative PGE2 at 4 and 24 h respectively was 10% ± 17% versus 11% ± 69%, P = 0.29 and 34% ± 19% versus 47% ± 18%, P = 0.15. We conclude that despite inhibiting the surgical stress response, PVAA had no effect on serum levels of putative breast cancer angiogenic factors, VEGF and PGE2.