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Objective: To evaluate nursing students' assessment and communication skills through an objective structured clinical examination (OSCE) within a high-fidelity simulation using a student-simulated patient (SSP) and analyze the validity, reliability, degree of difficulty, and discriminability of the OSCE. Methods: A descriptive study was conducted at one nursing school in Macao. All scenarios were designed using a high-fidelity simulator combined with SSPs. A convenience sample of 54 baccalaureate nursing students completed the OSCE. The nursing assessment OSCE checklist (NAOC) and the communication evaluation rubric (CER) were used as observational measurements with three-point Likert scales (2 = Achieved, 1 = Partly achieved, 0 = Not completed/Incorrect). Results: Difficulty coefficients of the exam were 0.63 for nursing assessment skills and 0.56 for communication skills. The discrimination index of the majority items of the NAOC (86.4％) was >0.20, showing a better to good discriminability. The items of the CER had satisfactory indexes of item discrimination (from 0.38 to 0.84). Students received high scores in conducting blood oxygen saturation and cardiac and lung auscultation but low scores in vomiting and diarrhea assessment. Students presented good communication skills in eye contacting and listening, but culture assessment needs to be improved. The students with experiences in simulation or simulated patient (SP) interactions had better assessment and communication skills than students without those experiences. There was a positive relationship between nursing assessment and communication skills (r = 0.67, P = 0.000). Conclusions: SSPs were involved in enhancing the realism of interactions in simulated scenarios. Nursing students can conduct nursing assessments specific to patient conditions, explain the conditions to the patient, and ensure that the patient remains informed at all times of the precautions to be taken. However, students' cultural awareness and some communication skills need fur ther training. With moderate difficulty and high discrimination index, OSCE showed satisfactory reliability and validity.