This study examined the effect of 12 weeks of small-sided street soccer (2.2 ± 0.7 sessions/week) and fitness center training (0.5 ± 0.2 sessions/week) on physical fitness and cardiovascular health profile for homeless men. Exercise capacity, maximal oxygen uptake (VO(2max)), body composition (DXA scans), blood pressure (BP), and blood lipid profile were determined before and after the intervention period for 22 soccer-group subjects (SG) and 10 waiting list controls (CO). In addition, time-motion analyses, HR measurements, and pedometer recordings were performed during street soccer training and daily-life activities. During a 60 min 4 versus 4 street soccer session 182 ± 62 intense running bouts were performed; mean HR was 82 ± 4% HR(max) and HR was >90% HR(max) for 21 ± 12% (±SD) of total time. On a day without training the participants performed 10,733 ± 4,341 steps and HR was >80% HR(max) for 2.4 ± 4.3 min. In SG, VO(2max) was elevated (p < 0.05) from 36.7 ± 7.6 to 40.6 ± 8.6 ml/min/kg after 12 weeks and incremental cycle test performance was improved (p < 0.05) by 81 s (95% CI: 47-128 s). After 12 weeks, fat percentage (19.4 ± 8.5 to 17.5 ± 8.6%) and LDL cholesterol (3.2 ± 1.1 to 2.8 ± 0.8 mmol L(-1)) were lowered (p < 0.05) in SG. The observed changes in SG were different (p < 0.05) from CO and no intra-group changes occurred for CO (p > 0.05). BP was unaltered after 12 weeks (p > 0.05), but diastolic BP was lowered for all SG subjects with pre-values >75 mmHg (83 ± 6 to 76 ± 6 mmHg, n = 8, p < 0.05). In conclusion, the exercise intensity is high during street soccer and regular street soccer training can be used as an effective activity to promote physical fitness and cardiovascular health status for homeless men.