Background and Objectives: Complex regional pain syndrome (CRPS) is defined as an extreme and chronic pain condition, and photobiomodulation has relevance as a complementary treatment for CRPS. The objective of this study was to verify the effects of photobiomodulation (PBMT) therapy protocols at two wavelengths 660 and 830 nm, associated or not to nicotine in complex regional pain syndrome type I (CRPS-I). Study Design/Materials and Methods: Sixty-four Swiss mice were divided into the following groups: (i) Naive, (ii) Sham, (iii) Control, (iv) 660 nm, (v) 830 nm, (vii) Nicotine, (vii) Nicotine/660 nm, and (viii) Nicotine/830 nm. CRPS-I was induced in an experimental ischemia/reperfusion model by affixing an elastic ring, proximal to the ankle joint of the right hind mouse paw, for 3 hours. Nicotine, in the respective groups was administered for 28 days prior to the induction of CRPS-I. PBMT was applied immediately after the procedure and for 20 consecutive days. The animals were evaluated for mechanical hyperalgesia, thermal hyperalgesia, paw edema at baseline and for 7, 14, and 21 days. Statistical analyses comprised a mixed-effects model, using the Tukey post hoc test (P < 0.05). Results: The PBMT wavelengths in 660 and 830 nm groups had beneficial effects (P < 0.05) in reducing mechanical and thermal hyperalgesia, but the effects at 660 nm were significantly better than 830 nm. At reducing edema, both wavelengths had significant effects statistically, absolutely no difference between them. Conclusions: The use of PBMT (660 and 830 nm) was effective in reducing mechanical hyperalgesia and thermal hyperalgesia; however, PBMT at 660 nm generated significant results. In reducing edema, both wavelengths had similar effects, which were significant statistically. The deleterious effects of nicotine were evident statistically and were softened when treated with PBMT (P < 0.05). Lasers Surg. Med.