Background and objective: Oxidative stress (OxS) is known to play a role in the etiopathogenesis of many diseases. Many studies have shown increased oxidative damage in various gastrointestinal (GI) diseases, but the mechanism of this in GI bleeding has not been fully explained. The aim of this study was to assess the levels of trace elements, ischemia-modified albumin (IMA), malondialdehyde (MDA), and vitamin C in the etiopathogenesis of GI hemorrhage. Materials and methods: Our study group consisted of 40 acute nonvariceal upper gastrointestinal bleeding (ANVUGIB) patients and 44 non-ulcer dyspepsia (NUD) subjects who underwent upper endoscopy. The whole blood count and biochemical parameters were measured by an automated analyzer. Trace elements were measured by inductively coupled plasma optical emission spectrometry (ICP-OES). Serum ischemia-modified albumin (IMA) was measured by albumin-cobalt binding (CAB) test. MDA levels were measured using a thiobarbituric acid reactive substances assay. The concentration of vitamin C in the serum was estimated by the phenylhydrazine spectrophotometry method. Results: The white blood cell (WBC) count (p < 0.005), prothrombin time (PT) (p < 0.001), and hemoglobin (Hb) (p < 0.001), alanine aminotransferase (ALT) (p < 0.008), albumin (Alb) (p < 0.001), vitamin C (p < 0.001), zinc (Zn) (p < 0.001), selenium (Se) (p < 0.001), and iron (Fe) (p < 0.004) levels were found lower in the ANVUGIB group than in the NUD group. However, the erythrocyte sedimentation rate (ESR) (p < 0011), international normalized ratio (INR) (p < 0.001), and creatinine (Cr) (p < 0.002), urea (p < 0.001), MDA (p < 0.001), IMA (p < 0.001), and copper (p < 0.018) levels were higher in the -ANVUGIB group than in the NUD group. Conclusion: Our results showed that together with trace elements, oxidative damage and ischemia were involved in the etiopathogenesis of ANVUGIB. Further studies are required to clarify the details of the mechanisms underlying the disease.